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Text : Radiotherapy has been widely used for the treatment of cancer patients, especially for esophageal cancer patients. Ring finger protein 2 (RNF2) plays an important role in promoting the growth of cancer cells after exposure to irradiation. The present study aims to characterize the proliferative effects of RNF2 on cancer cells, and its mechanisms on the growth of esophageal cancer cells. We demonstrate that expression of RNF2 was markedly upregulated in esophageal cancer cell lines and surgically resected cancer specimens. In addition, RNF2 expression level is positively correlated with the presence of tumor size, lymph node metastases and negatively correlated with patient survival rates, suggesting that it plays an important role in the progression of esophageal cancer. Furthermore, the expression of RNF2 at both mRNA and protein levels in esophageal cancer ECA109 and TE13 cells was detected by real-time PCR and western blot assay after shRNA targeting RNF2. Co-immunoprecipitation (Co-IP) assay and western blot analysis were employed to detect the interaction between RNF2 and r-H2AX, H2AK119ub, and the expression of proteins associated with cell cycle and apoptosis, respectively. We used flow cytometry assay to analyze cell cycle and apoptosis of transfected cells, and further examined cellular growth in vitro and in vivo. shRNA targeting RNF2 gene and protein downregulated RNF2 expression after transfection for 24 h. The proliferation of tumor cells in RNF2-shRNA group was suppressed after radiotherapy. In addition, the interaction of RNF2, H2AK119ub, r-H2AX was increased after exposure to IR, followed by increasing apoptosis rates and inducing the arrest at G0/G1 phase after irradiation and shRNA targeting RNF2. Expression of the short-hairpin RNA is also correlated with the upregulation of p16 and Bax, and the downregulation of cyclin D2, cyclin-dependent kinase (CDK)-4, H2AX and Bcl-2. RNF2 gene knockdown induces radiosensitivity of esophageal cancer cells in vitro and significantly inhibits the growth of tumor cells. The mechanisms include inducing the cell cycle arrest at G0/G1 phase and promoting apoptosis. | Authentic |
Text : Cancer stem cells obtain energy demand through the activation of glycolysis and lipolysis. It seems that the use of approached targeting glycolysis and lipolysis could be an effective strategy for the inhibition of cancer stem cells. In the current experiment, we studied the potential effect of glycolysis and lipolysis inhibition on cancer stem cells differentiation and mesenchymal-epithelial-transition capacity. Cancer stem cells were enriched from human ovarian cells namely SKOV3 by using MACS technique. Cells were exposed to Lonidamine, an inhibitor of glycolysis, and TOFA, a potent inhibitor of lipolysis for 7 days in endothelial differentiation medium; EGM-2 and cell viability was studied by MTT assay. At the respective time point, the transcription level of genes participating in EMT such as Zeb-1, -2, Vimentin, Snail-1, -2 and VE-cadherin were measured by real-time PCR analysis. Our data noted that the inhibition of lipolysis and glycolysis could decrease cell viability compared to the control of cancer stem cells. The inhibition of glycolysis prohibited the expression of Zeb-1, Snails, and Vimentin while increased endothelial differentiation rate indicated by the expression of VE-cadherin. In contrast, the inhibition of lipolysis increased EMT associated genes and reduced endothelial differentiation rate by suppressing the transcription of VE-cadherin. Notably, the simultaneous inhibition of glycolysis and lipolysis had moderate effects on the transcription of EMT genes. We concluded that the modulation of the metabolic pathway of glycolysis in ovarian CSCs is more effective than the inhibition of lipolysis in the control of angiogenesis potential and stemness feature. | Authentic |
Text : Copper transporter 1 (CTR1) plays an important role in increasing cisplatin intake. Our previous studies showed that CTR1 expression was upregulated by (-)-epigallocatechin-3-gallate (EGCG), a green tea polyphenol, therefore enhanced cisplatin sensitivity in ovary cancer and non-small-cell lung cancer (NSCLC) cells. In the current study in the non-small-cell lung cancer cells, we uncovered a potential mechanism of EGCG-induced CTR1 through its pro-oxidative property. We found that EGCG increased reactive oxygen species (ROS) generation, while in the presence of ROS scavenger N-acetyl-cysteine (NAC), ROS production was eliminated. Changes of CTR1 expression were consistent with the ROS level. Simultaneously, EGCG downregulated ERK1/2 while upregulated lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) through ROS to induce CTR1 expression. Besides, in a nude mouse xenografts model, EGCG treatment raised ROS level, expression of CTR1 and NEAT1 in tumor tissue. Also, ERK1/2 and p-ERK1/2 were suppressed as well. Taken together, these results suggested a novel mechanism that EGCG mediated ROS to regulate CTR1 expression through the ERK1/2/NEAT1 signaling pathway, which provided more possibilities for EGCG as a natural agent in adjuvant therapy of lung cancer. | Authentic |
Text : Leukemia is one of the severe cancer types all around the globe. Even though some chemotherapeutic drugs are available for treating leukemia, they have various side effects. As an alternative approach, herbal drugs are focused on current research to overcome leukemia. The present work was conducted to investigate the antileukemic mechanism of active phytochemical vitexin, which was isolated from ethno-medicine (Prosopis cineraria leaf) used by traditional healers of West Bengal, India. Antiproliferative mechanisms of selected phyto-compound against K-562 cells were evaluated using cellular uptake, morphological changes, DNA fragmentation, mitochondrial membrane potential and signaling pathways analysis. Vitexin exhibited cytotoxicity by reducing mitochondrial membrane potential (32.40%) and causing DNA fragmentation (84.15%). The western blotting study indicated inhibition of cell survival proteins (BCR, ABL, H-RAS, N-RAS, K-RAS and RAF) and expression of apoptotic proteins (p38, BAX and caspase-9) in leukemia cells upon treatment with vitexin. Based on the results, presently investigated phyto-compound vitexin could be considered for developing safe and natural drugs to treat leukemia after conducting suitable preclinical and clinical trials. | Authentic |
Text : The rationale of designing compounds containing a (3,4,5-trimethoxybenzyloxy) phenyl moiety is largely due to its potential antioxidant and cytotoxic activities. A previous study focused on its antioxidant mechanism, whereas in this study, we investigated the cytotoxicity of a series of 28 analogues and the mechanism of apoptosis of the most cytotoxic compound against wild-type (HCT-116) and p53 mutant (HT-29) colorectal cancer cell lines. The series of analogues comprise of different families, namely hydrazone, oxadiazole, thiosemicarbazides and triazoles. In the initial cytotoxicity screening, N-(3,4,5-trimethoxybenzylidene)-4-(3,4,5-trimethoxybenzyloxy) benzohydrazide, henceforth known as, P5H, was found to be most cytotoxic against human colorectal cancer cell lines (IC50 for HCT-116 = 11.79 μM and HT-29 = 18.52 μM). Additionally, P5H was found to have some degree of selectivity towards cancer cells compared to normal human colon cells (CCD-112 CoN). Subsequent investigation had brought insight on P5H ability to induce apoptosis in both HCT-116 and HT-29 cell lines. Cell cycle analysis showed both cell lines were arrested at the G2/M phase upon treatment. Our study concluded that P5H induced the death receptor, DR5 in HCT-116 and mitochondria-mediated apoptosis pathway in HT-29. Therefore, P5H may be a promising candidate as a chemotherapy agent against colon cancer. Graphical abstract The apoptotic pathways induced in HT-29 and HCT-116 cells upon P5H treatment. | Authentic |
Text : Fibroblast growth factor 21 (FGF21) as a member of the FGFs serves a key role in glucose homeostasis and protection of the liver, heart, kidney and skin from damage as well as cancer cell development. In addition, transcription of FGF21 is sensitive to diverse damages; however, the role of the transcriptional regulator of FGF21 in cancer cells remains to be elucidated. FGFs were identified to have dominant expression in cancer cells; therefore, mouse forestomach carcinoma (MFC) cells were used in the present study, which is a mouse stomach cancer cell strain for identifying the FGF21 regulators. In promoter analysis of FGF21, the putative transcription factor 4 (TCF4) binding motifs (T/AC/GAAAG) were observed within 1.5 kb of the promoter region. Further chromatin immunoprecipitation and yeast-one hybrid assays identified that TCF4 directly bound to one of the two putative binding motifs observed. A co-immunoprecipitation assay identified that β-catenin interacts with TCF4 in MFC cells, and the β-catenin/TCF4 complex bound to the promoter of FGF21. In order to examine the function of TCF4 and β-catenin in transcriptional regulation of FGF21, TCF4 and β-catenin was transiently expressed in MFC cells. Reverse transcription-quantitative polymerase chain reaction results revealed that overexpression of TCF4 and β-catenin activated FGF21 transcription. Besides, suppression of β-catenin via a specific short interfering RNA resulted in reduction of FGF21 expression. Together these findings suggest that the β-catenin/TCF complex directly activates FGF21 via promoter binding. The observations of the present study may help elucidate the regulatory mechanism of FGF21, which is a key pharmaceutical protein. | Authentic |
Text : Gefitinib (GEB) is one of the drugs used for patients with epidermal growth factor receptor (EGFR)-positive mutations in non-small cell lung cancer (NSCLC). However, application of GEB is limited by its low water solubility, stability, and utilization rate, especially the side effects while GEB is given by oral. In this study, nanoliposome was used as a carrier to prepare nanoliposome compound drug (GL) by embedding GEB in the nanoliposome perfectly combined with green nontoxic solvent and thin-film dispersion method. The nanoliposome structure was expected to improve the water solubility and biocompatibility of GEB, thus improving the effect of cancer treatment. The surface electronegative nanoliposomes can effectively avoid protein adsorption and prolong the circulation time in vivo. Meanwhile, the ratio of lecithin to cholesterol (LE/CH) was explored to maximize the encapsulation efficiency of nanoliposome. Subsequent test results showed that GL exhibited better stability, smaller particle size and higher encapsulation efficiency. In addition, in vitro drug release curve also further confirmed that GL had a promising drug sustained-release effect. In particular, a series of in vitro tests such as cell activity, apoptosis, colony formation, scratch, invasion, and cell cycle assays were performed. The results indicated that GL significantly enhanced the pro-apoptotic effect on A549 cells. Most cell cycles of A549 cells were blocked in the G0/G1 phase influenced by GL, thus inhibiting the proliferation of cancer cells. In vivo anti-tumor studies showed that compared with pure GEB, GL had a significant inhibiting effect on NSCLC. In conclusion, the GL which was synthesized by a simple method in this study significantly improved the treatment effect of cancer cells, which proved that the nanoliposome carrier had an excellent application prospect in the treatment of lung cancer. | Authentic |
Text : This study aims to investigate long non-coding RNA LINC01133 (LINC01133) expressions in colorectal cancer (CRC) patients, and discuss its correlation with CRC clinicopathological features and prognosis. qRT-PCR was performed to measure expression levels of LINC01133 in CRC tissues. The chi-square test was used to assess LINC01133 expression with respect to clinicopathological parameters. Kaplan-Meier analysis and the log-rank test were performed to identify survival differences in CRC patients. Univariate and multivariate analysis were performed using the Cox proportional hazard analysis. LINC01133 was significantly down-regulated in CRC tissues compared to normal tissue samples (p < 0.001), and a low expression of LINC01133 was found to be significantly associated with lymph node metastasis (p = 0.004), distant metastasis (p = 0.043), N classification (p = 0.022) and TNM stage (p = 0.011). Moreover, Kaplan-Meier survival analysis revealed that high LINC01133 expression predicted significantly better overall survival (p = 0.0093). Finally, multivariate analysis results indicated that LINC01133 was an independent prognostic factor in CRC. Our results indicated that reduced LINC01133 expression contributed to CRC metastasis and poor prognosis. Thus, LINC01133 might serve as a promising biomarker for prognosis of CRC. | Authentic |
Text : Hepatocellular carcinoma (HCC) is a primary liver tumor and is the most difficult human malignancy to treat. In this study, we sought to develop an integrative approach in which real-time tumor monitoring, gene therapy, and internal radiotherapy can be performed simultaneously. This was achieved through targeting HCC with superparamagnetic iron oxide nanoparticles (SPIOs) carrying small interfering RNA with radiolabled iodine 131 (131I) against the human vascular endothelial growth factor (hVEGF). hVEGF siRNA was labeled with 131I by the Bolton-Hunter method and conjugated to SilenceMag, a type of SPIOs. 131I-hVEGF siRNA/SilenceMag was then subcutaneously injected into nude mice with HCC tumors exposed to an external magnetic field (EMF). The biodistribution and cytotoxicity of 131I-hVEGF siRNA/SilenceMag was assessed by SPECT (Single-Photon Emission Computed Tomography) and MRI (Magnetic Resonance Imaging) studies and blood kinetics analysis. The body weight and tumor size of nude mice bearing HCC were measured daily for the 4-week duration of the experiment. 131I-hVEGF siRNA/SilenceMag was successfully labeled; with a satisfactory radiochemical purity (>80%) and biological activity in vitro. External application of an EMF successfully attracted and retained more 131I-hVEGF siRNA/SilenceMag in HCC tumors as shown by SPECT, MRI and biodistribution studies. The tumors treated with 131I-hVEGF siRNA/SilenceMag grew nearly 50% slower in the presence of EMF than those without EMF and the control. Immunohistochemical assay confirmed that the tumor targeted by 131I-hVEGF siRNA/SilenceMag guided by an EMF had a lower VEGF protein level compared to that without EMF exposure and the control. EMF-guided 131I-hVEGF siRNA/SilenceMag exhibited an antitumor effect. The synergic therapy of 131I-hVEGF siRNA/SilenceMag might be a promising future treatment option against HCC with the dual functional properties of tumor therapy and imaging. | Authentic |
Text : The aim of this study was to investigate the expression and clinical significance of hPTTG1 in gastric cancer. Immunohistochemistry was performed to determine the expression of hPTTG1 in gastric cancer tissues. Results showed that the positive expression of hPTTG1 in gastric cancer tissues was 60.00%, while in adjacent normal tissues it was 17.78%. The expression of hPTTG1 was correlated with differentiation levels, clinical classification and lymph node metastasis, but did not correlate with gender, age or pathological types. hPTTG1 was, therefore, overexpressed in gastric cancer tissues. The progression of gastric cancer was found to be correlated with the upregulation of the expression of hPTTG1. hPTTG1 detection may be helpful in evaluating the ability of the clinical classification and lymph node metastasis in gastric cancer to predict outcomes. These factors act as indicators of the biological behavior of gastric cancer and are fairly good markers for prognosis and therapy. | Authentic |
Text : Circular RNAs (circRNAs), a recently identified new member of non-coding RNAs, are demonstrated to participate in diverse biological processes; however, the molecular mechanisms that link circRNAs with colorectal cancer (CRC) are not well understood. In the present study, we attempted to explore the roles of the exosomal circRNAs on CRC progression. We first compared the expression patterns of exosomal circRNAs between the plasma of CRC patients and healthy controls. We identified 448 significantly dysregulated exosomal circRNAs in CRC plasma. We focused on hsa_circ_0067835, which is located on chromosome 3 and derived from IFT80; thus, we named it circIFT80. Then, the expression of circIFT80 was detected in 58 CRC tissues and cell lines by qRT-PCR. Functional assays were performed to evaluate the effects of circIFT80 on tumor growth in vitro and in vivo. The relationship between circIFT80 and miR-1236-3p was confirmed by luciferase reporter assay. We found that circIFT80 was significantly upregulated in CRC serum exosomes, CRC tissues, and CRC cell lines compared with normal control. Silencing circIFT80 suppressed CRC cell growth both in vitro and in vivo. We further demonstrated that circIFT80/miR-1236-3p/HOXB7 axis plays an important role in regulating CRC progression. Dual-luciferase reporter system validated the direct interaction of circIFT80, miR-1236-3p, and HOXB7. Western blot verified that inhibition of circIFT80 decreased HOXB7 expression, while a miR-1236-3p inhibitor attenuated the effect of inhibition of circIFT80. In conclusion, these data suggest that circIFT80 is a central component linking circRNAs to the progression of CRC via a miR-1236-3p/HOXB7 axis. | Authentic |
Text : Non-small-cell lung cancer (NSCLC) is a major health problem that endangers human health. The prognosis of radiotherapy or chemotherapy is still unsatisfactory. This study is aimed at investigating the predictive value of glycolysis-related genes (GRGs) on the prognosis of NSCLC patients with radiotherapy or chemotherapy. Download the clinical information and RNA data of NSCLC patients receiving radiotherapy or chemotherapy from TCGA and geo databases and obtain GRGs from MsigDB. The two clusters were identified by consistent cluster analysis, the potential mechanism was explored by KEGG and GO enrichment analyses, and the immune status was evaluated by estimate, TIMER, and quanTIseq algorithms. Lasso algorithm is used to build the corresponding prognostic risk model. Two clusters with different GRG expression were identified. The high-expression subgroup had poor overall survival. The results of KEGG and GO enrichment analyses suggest that the differential genes of the two clusters are mainly reflected in metabolic and immune-related pathways. The risk model constructed with GRGs can effectively predict the prognosis. The nomogram combined with the model and clinical characteristics has good clinical application potential. In this study, we found that GRGs are associated with tumor immune status and can assess the prognosis of NSCLC patients receiving radiotherapy or chemotherapy. | Authentic |
Text : Preliminary analysis of breast cancer related to unknown functional gene FAM83A through bioinformatics knowledge to inform further experimental studies. Select high expression genes for breast cancer and use bioinformatics methods to predict the biological function of FAM83A. Genes with significant differences in expression between breast tumors and normal breast tissue libraries were selected from CGAP's SAGE Digital Gene Expression Displayer (DGED) database. An unknown functional gene, FAM83A, which is highly expressed in breast cancer, was screened. We performed an analysis of the gene structure, subcellular localization, physicochemical properties of the encoding products, functional sites, protein structure, and functional domains. Through SAGE DGED, a total of 185 genes with expression differences were found. The structure and function of FAM83A have ideal predictions, and it is generally determined that this gene encodes a nuclear protein with a nucleoprotein. The active site of PLDc and the functional domain of DUF1669 can be involved in signal transduction and gene expression regulation in tumorigenesis and metastasis. Digital gene representation of the Tumor Genome Project Data Library was used to select differentially expressed genes in breast cancer tissue and breast benign tumor tissue. Studies show that FAM83A is a potential research target associated with tumorigenesis and metastasis. Initial tests confirmed the expression of this gene. Lay a solid foundation for further research learning. FAM83A is a highly expressed gene in breast cancer and can serve as a target for studying molecular mechanisms in breast cancer. | Authentic |
Text : The objective of this paper was to assess the effects of hydatid cyst fluid (HCF) of Echinococcus granulosus on melanoma A375 cell proliferation and apoptosis. A375 cells were classified into five groups by in vitro culture: normal group, control group, 10% HCF group, 20% HCF group and 30% HCF group. Trypan blue staining method was employed to detect the toxicity of HCF. Effects of different concentrations of HCF on melanoma A375 cell proliferation at different time points were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Flow cytometry and propidium iodide (PI) staining were used to detect cell cycle, and Annexin-V/PI double staining method was used to determine A375 cell apoptotic rate. Western blotting was applied to detect the expression of phosphorylated extracellular regulated protein kinases, proliferating cell nuclear antigen (PCNA), cell-cycle-related proteins (cyclin A, cyclin B1, cyclin D1 and cyclin E) and apoptosis-related proteins (Bcl-2, Bax and caspase-3). HCF with a high concentration was considered as atoxic to A375 cells. HCF promoted A375 cell proliferation, and the effects got stronger with an increase in concentrations but was retarded after reaching a certain range of concentrations. HCF increased phosphorylation level and expression of extracellular regulated protein kinase, as well as PCNA expression. HCF also promoted the transferring progression of A375 cells from the G0/G1 phase to the S phase to increase the cell number in S phase and increased the expression of cyclin A, cyclin D1 and cyclin E. HCF increased the expression of procaspase-3 (the precursor of apoptosis-related protein caspase-3) and antiapoptotic protein-Bcl-2, and decreased the expression of proapoptotic factor Bax, thereby inhibiting cell apoptosis. As a result, this study confirmed that HCF promotes proliferation and inhibits apoptosis of melanoma A375 cells. | Counterfeit |
Text : Biosynthesis of silver nanoparticles (AgNPs) from the medicinal plants has been considered as a remarkable approach of several therapeutic innovations and successful drug delivery. Silver nanoparticles were biosynthesized with Salvia miltiorrhiza, Chinese medicinal herb and assessed for its anticarcinogenic property. Synthesis of AgNPs was characterized by several studies such as UV-absorbance and it shows peak values in the range of 425-445 nm. The sizes of the nanoparticles are confirmed by dynamic light scattering analysis and it shows 100 nm. Furthermore, transmission electron microscopy (TEM) and energy dispersive X-ray analysis (EDX) was to confirm the shape and Ag particles are present in the synthesized materials. FTIR analysis to find out the active biomolecules located in the surface of the synthesized particles. This AgNPs from S. miltiorrhiza inhibits the growth of Bacillus subtillis, Staphylococcus aureus, Escherichia coli, and Klebsiella pneumonia. Furthermore, the anticancer potential of AgNPs is examined in prostate adenocarcinoma (LNCaP) cell lines. In this study, we found the AgNPs effectively induces cytotoxicity, ROS and apoptosis by modulation of intrinsic apoptoic Bcl2, Bclxl, Bax and Caspase 3 protein expressions in LNCap cell lines. Based on the study, synthesis of AgNPs from S. miltiorrhiza shows eco-friendly and it exhibits antimicrobial and anticarcinogenic effects. | Authentic |
Text : Previous studies have indicated that high expression of lactate dehydrogenase A (LDHA) exists in many human cancers. Recently, several reports showed that silencing or inhibition of LDHA could suppress metastasis of human cancer including renal cell carcinoma (RCC). However, the mechanism remains unknown. The role of LDHA in RCC migration and invasion was investigated using immunohistochemistry, western blotting, Transwell and scratch assays, and in vivo experiment. The influence of LDHA on the Warburg effect was also investigated by LDHA activity and lactate production assay. LDHA was overexpressed in RCC tissues and predicted a worse survival following renal resection. Correlation analysis demonstrated that LDHA was negatively correlated with E‑cadherin and positively with N‑cadherin. Experimentally, both in vivo and in vitro experiments found downregulation of LDHA suppressed RCC cells migration and invasion by inhibiting EMT. In addition, results indicated LDHA could promote the Warburg effect. Further research presented that the LDHA inhibitor, oxamate, suppressed tumor metastasis by inhibiting LDHA activity and EMT. These results demonstrated that LDHA mediates tumor metastasis by promoting EMT in RCC, suggesting that LDHA could be a promising therapeutic target for RCC therapy. | Authentic |
Text : Prostate cancer poses a major public health problem in men. Metastatic prostate cancer is incurable, and ultimately threatens the life of patients. Lysine‑specific demethylase 1 (LSD1) is an androgen receptor‑interacting protein that exerts a key role in regulating gene expression and is involved in numerous biological processes associated with prostate cancer. Cisplatin, also known as cis‑diamminedichloroplatinum or DDP, is a standard chemotherapeutic agent used to treat prostate cancer; however, it has the disadvantage of various serious side effects. The present study aimed to investigate the effects of LSD1 knockdown, and the interplay between LSD1 and DDP, on prostate cancer cell proliferation, apoptosis and invasion, and, therefore, the potential of LSD1 as a target for prostate cancer therapy. Flow cytometric analysis, Cell Counting kit 8 assay, Transwell assay and western blotting results revealed that LSD1 knockdown, in combination with DDP treatment, exerted antiproliferative, proapoptotic and anti‑invasive effects on PC3 prostate cancer cells. In addition, knockdown of LSD1 acted synergistically with DDP, thereby enhancing the induction of apoptosis, and the inhibition of proliferation and invasion in prostate cancer cells. These results indicated that LSD1 may serve as a potential therapeutic target, and may enhance the sensitivity of PC3 cells to DDP. | Counterfeit |
Text : The use of poly(ethylene glycol) (PEG) for the development of novel PEGylated biomolecules is playing an increasingly meaningful role in cancer treatment. Cisplatin (CDDP), is a useful chemotherapy drug. However, it is unclear whether PEGylated cisplatin (CDDPPEG) has potential as an alternative therapeutic agent. Here we prepared a PEGylated cisplatin by gamma radiation-induced synthesis, for the first time. PEGylated drugs were characterized using Raman and Fourier transform infrared spectroscopy (FTIR), as well as scanning electron microscopy coupled with Energy Dispersive X-ray (SEM/EDX). The results show that the cisplatin can be successfully PEGylated by this method. Furthermore, we show a proposal for the mechanism of the PEGylation reaction. The novel product exhibits in vitro therapeutic potential comparable to cisplatin at concentrations lower than 23 μM (Pt), causing differences in cell cycle checkpoints, which suggest changes in the signaling pathways that control growth arrest and cause apoptosis of A549 cells. | Authentic |
Text : Lung cancer is a leading cause of cancer-associated mortality worldwide, which has a low survival rate. Multidrug resistance (MDR) is a major obstacle that hinders the treatment of lung cancer. Doxorubicin (DOX) is an anthracycline glycoside antibiotic, having a broad spectrum of anticancer activity against various solid tumors. Juglanin is a natural production, mainly extracted from green walnut husks of Juglans mandshurica, exhibiting various bioactivities. Here, we demonstrated that the combination of drug, gene and nanoparticle overcame MDR, inhibiting lung cancer progression. A novel nanoparticular pre-chemosensitizer was applied to develop a self-assembled nanoparticle formula of amphiphilic poly(juglanin (Jug) dithiodipropionic acid (DA))-b-poly(ethylene glycol) (PEG)-siRNA Kras with DOX in the core (DOX/PJAD-PEG-siRNA). The formed nanoparticles, appeared spherical shape, had mean particle size of 81.8 nm, and the zeta potential was -18.62 mV. The in vitro drug release results suggested that a sustained release was observed in DOX/PJAD-PEG-siRNA nanoparticles compared to the free DOX. Jug could improve the cytotoxicity of DOX to cancer cells with MDR. Oncogene, Kras, was dose-dependently reduced by treatment of DOX/PJAD-PEG-siRNA nanoparticles. Additionally, P-glycoprotein (MDR1) and c-Myc, contributing to tumor progression, were suppressed by the nanoparticles, while p53 was improved in drug-resistant cells. Colony formation analysis suggested that DOX/PJAD-PEG-siRNA nanoparticles showed the most effective role in reducing cancer cell proliferation. In vivo, DOX/PJAD-PEG-siRNA nanoparticles reduced tumor growth compared to the free DOX, accompanied with reduced KI-67 and enhanced TUNEL positive levels in drug-resistant xenografted nude mice. Thus, the findings above indicated that juglanin, as a chemosensitizer, potentiate the anti-cancer role of DOX in drug-resistant cancer cells. And the nanoparticles exhibited stronger antitumor efficiency, suggesting potential value in the treatment of lung cancer. | Authentic |
Text : Cervical cancer is one of most malignant gynecological tumors. However, effective means for diagnosing and treating cervical cancer have yet to be identified. A few decades ago, long non-coding RNAs (lncRNAs) were regarded as useless parts of the genome, however, increasing data have demonstrated the importance of lncRNAs in the diagnosis and treatment of cervical cancers. The aim of the present study is to summarize the role(s) of HOTAIR, MALAT1, CCAT2, SPRY4-IT1, RSU1P2, CCHE1, lncRNA-EBIC and PVT1. Approximately 14 lncRNAs are involved in cervical cancer and several important proteins, miRNAs and other molecules and play crucial roles in a few traditional signaling pathways that have been proven to be related to those lncRNAs. In conclusion, lncRNAs may be useful as exact treatment targets and diagnostic biomarkers for improving therapies in cervical cancer patients and lncRNAs may contribute to effective diagnosis and treatment methods for cervical cancer. | Authentic |
Text : A cancer microenvironment generates strong hydrogen bond network system by the positive feedback loops supporting cancer complexity and robustness. Such network functions through the AKT locus generating high entropic energy supporting cancer metastatic robustness. Charged lepton particle muon follows the rule of Bragg effect during a collision with hydrogen network in cancer cells. Muon beam dismantles hydrogen bond network in cancer by the muon-catalyzed fusion, leading to apoptosis of cancer cells. Muon induces cumulative energy appearance on the hydrogen bond network in a cancer cell with its fast decay to an electron and two neutrinos. Thus, muon beam, muonic atom, muon neutrino shower, and electrons simultaneously cause fast neutralization of the AKT hydrogen bond network by the conversion of hydrogen into deuterium or helium, inactivating the hydrogen bond networks and inducing failure of cancer complexity and robustness with the disappearance of a malignant phenotype. | Authentic |
Text : MicroRNAs (miRNAs) have been shown to participate in the development of pancreatic ductal adenocarcinoma (PDAC) by modulating multiple cellular processes. Increased miR-224 expression enhances proliferation and metastasis in human cancers. This study aimed to investigate the role of miR-224 and its underlying mechanism of action in PDAC. BrdU, MTT, and cell migration assays were performed to determine cell proliferation, viability, and migration, respectively. The binding sites of miR-224 were identified using a luciferase reporter system, whereas protein expression of target genes was determined by immunoblotting and immunofluorescence analyses. A BALB/c nude mouse xenograft model was used to evaluate the role of miR-224 in vivo. We demonstrated that miR-224 expression was enhanced in PDAC cells and tissues, and was related to migration and proliferation. Noticeably, miR-224 overexpression promoted the proliferation, migration, and metastasis of Panc1 cells, while miR-224 inhibition had the reverse effect on PDAC cells. Moreover, we found that thioredoxin-interacting protein (TXNIP) is a target of miR-224. The results also indicated that miR-224 inversely regulated TXNIP by binding directly to its 3'-untranslated region, which resulted in the activation of hypoxia-inducible factor 1α (HIF1α). Further, either TXNIP re-expression or HIF1α depletion abolished the effects of miR-224 on the proliferation and migration of PDAC cells in vitro and in vivo. Regarding the relationship of TXNIP and HIF1α, we found that TXNIP mediated the nuclear export of HIF1α and its degradation by forming a complex with HIF1α. The miR-224-TXNIP-HIF1α axis may be useful in developing novel therapies for PDAC. | Authentic |
Text : This study aimed to explore the underlying microRNA (miRNA) targets in clear cell renal cell carcinoma (ccRCC). The expression profile with accession number GSE24952 was downloaded from the Gene Expression Omnibus database. Based on the dataset, the differentially expressed genes (DEGs) and miRNAs in ccRCC tissues and matched normal adjacent tissues were analyzed. The target genes of the differentially expressed miRNAs were then predicted. Expression levels of several key miRNAs and genes were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). A total of 168 up- and 288 downregulated DEGs, and 26 up- and 54 downregulated differentially expressed miRNAs were identified. The target genes of miRNA-429 (TGFB1, CCND1, EGFR, and LAMC1) and miRNA-206 (CCND1 and EGFR) were upregulated. Based on the tumor suppressor (TS) gene and tumor-associated gene (TAG) databases, miRNA-142-5p was selected from the upregulated miRNAs. miRNA-429, miRNA-422a, miRNA-206, miRNA-132-3p, and miRNA-184 were selected from the downregulated miRNAs. Moreover, the miRNA regulation network revealed that CCND1 was the common target gene of miRNA-429, miRNA-206, and miRNA-184, and ATP1B1 was the common target gene of miRNA-140-3p and miRNA-142-5p. qRT-PCR revealed that the expression levels of miR-140-3p and CCND1 significantly increased, while that of ATP1B1 significantly decreased in 786-O cells compared with those in human renal tubular epithelial cells, which was in accordance with the predicted results of bioinformatic analysis. In conclusion, miRNA-429, miRNA-206, and miRNA-184 and their target gene CCND1, as well as miRNA-140-3p and miRNA-142-5p and their target gene ATP1B1, might play key roles in ccRCC progression and could be useful biomarkers during ccRCC development. | Authentic |
Text : Both preclinical and epidemiology studies associate β-adrenoceptors-blockers (β-blockers) with activity against melanoma. However, the underlying mechanism is still unclear, especially in acral melanoma. In this study, we explored the effect of propranolol, a non-selective β-blocker, on the A375 melanoma cell line, two primary acral melanoma cell lines (P-3, P-6) and mice xenografts. Cell viability assay demonstrated that 50μM-400μM of propranolol inhibited viability in a concentration and time dependent manner with an IC50 ranging from 65.33μM to 148.60μM for 24h -72h treatment, but propranolol (less than 200μM) had no effect on HaCaT cell line. Western blots showed 100μM propranolol significantly reduced the expression of Bcl-2 while increasing the expressions of Bax, cytochrome c, cleaved capase-9 and cleaved caspase-3, and down-regulated the levels of p-AKT, p-BRAF, p-MEK1/2 and p-ERK1/2 in melanoma cells, after a 24h incubation. The in vivo data confirmed the isolation results. Mice received daily ip. administration of propranolol at the dose of 2 mg/kg for 3 weeks and the control group was treated with the same volume of saline. The mean tumor volume at day 21 in A375 xenografts was 82.33 ± 3.75mm3vs. 2044.67 ± 54.57mm3 for the propranolol-treated mice and the control group, respectively, and 31.66 ± 4.67 mm3vs. 1074.67 ± 32.17 mm3 for the P-3 xenografts. Propranolol also reduced Ki67, inhibited phosphorylation of AKT, BRAF, MEK1/2 and ERK1/2 in xenografts. These are the first data to demonstrate that propranolol might inhibit melanoma by activating the intrinsic apoptosis pathway and inactivating the MAPK and AKT pathways. | Authentic |
Text : Hepatocellular carcinoma (HCC) remains among the most lethal of human cancers, despite recent advances in modern medicine. miR-30c-5p is frequently dysregulated in different diseases. However, the effects and the underlying mechanism of miR-30c-5p in HCC are still elusive. Here, we show that miR-30c-5p is downregulated in HCC and significantly associated with survival and tumor size in patients with HCC. We demonstrate that aberrant miR-30c-5p markedly affects HCC cell proliferation and migration. Further experiments show that RAB32 is an essential target of miR-30c-5p in HCC. These studies highlight an important role of miR-30c-5p in growth and invasion of HCC and indicate that the miR-30c-5p-RAB32 axis is an important underlying mechanism. | Authentic |
Text : Gastric cancer as a common human malignancy has been associated with aberrant expressions of several coding and non-coding genes. Long non-coding RNAs (lncRNAs) as regulators of gene expressions at different genomic, transcriptomic and post-transcriptomic levels are among putative biomarkers and therapeutic targets in gastric cancer. In the present study, we have searched available literature and listed lncRNAs that are involved in the pathogenesis of gastric cancer. In addition, we discuss associations between expressions of these lncRNAs and tumoral features or risk factors for gastric cancer. Based on the established role of lncRNAs in regulation of genomic stability, cell cycle, apoptosis, angiogenesis and other aspects of cell physiology, the potential of these transcripts as therapeutic targets in gastric cancer should be evaluated in future studies. | Authentic |
Text : MicroRNA-19b (miR‑19b) is part of the miR‑17‑92 cluster which is associated with cardiac development. It has previously been reported that the overexpression of miR‑19b increases proliferation, inhibits apoptosis and promotes differentiation of embryonic carcinoma cells (P19 cells). The aim of the current study was to investigate the effects of miR‑19b knockdown on the proliferation, apoptosis, differentiation and regulation of the Wnt/β‑catenin signaling pathway in P19 cells. P19 cells were transfected with an miR‑19b knockdown plasmid or an empty vector. MiR‑19b knockdown or vector control stable cell lines were selected using puromycin. Cell Counting kit‑8 and flow cytometry were used to analyze the levels of cellular proliferation, cell cycle progression and the levels of apoptosis, respectively. Caspase‑3 activity and mitochondrial function assays were also used to analyze apoptosis. An inverted microscope was used to observe the morphological changes of P19 cells during differentiation. Reverse transcription‑quantitative polymerase chain reaction and western blot analysis were used to detect P19 cell differentiation markers and Wnt/β‑catenin signaling pathway‑related genes and their corresponding proteins. The results demonstrated that miR‑19b knockdown inhibited the proliferation and apoptosis of P19 cells. However, the levels of expression of Wnt and β‑catenin increased. MiR‑19b knockdown activated the Wnt/β‑catenin signaling pathway, which may regulate cardiomyocyte differentiation. The results of this study indicate that miR‑19b is a novel therapeutic target for cardiovascular diseases and provide insight into the mechanisms underlying congenital heart diseases. | Authentic |
Text : Cervical cancer is one of the most fatal malignancies in females. Acquired resistance to chemotherapeutic agent is one reason behind this lethality. In this study, we developed cisplatin resistance cell line, subsequently examined the molecular mechanisms linked. Transcriptome sequencing technology was utilized to compare the various expression models between the cisplatin-resistant cell line (Hela/DDP) and its parental cell line human cervical adenocarcinoma Hela. The present study has identified 2,312 differentially expressed genes (DEGs). Results showed there were 1,437 up-regulated genes and 875 down-regulated ones. Databases analysis including Gene ontology (GO), Cluster of Orthologous Groups of proteins (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed to reveal potential molecular mechanisms. We studied AKT3, a crucial gene in the PI3K/AKT pathway which clustered the most DEGs. Silencing AKT3 in Hela/DDP could enhance its sensibility to cisplatin. Quantitative real-time reverse transcription PCR (qRT-PCR) and western blot experiments were showed that expression of AKT3 was decreased after siRNA interference and inhibitor treatment. CCK-8 experiments showed that low expression of Akt3/pAkt enhanced the sensitivity of drug-resistant cells to cisplatin. Apoptotic analysis demonstrated that inhibition of AKT3 increased the rate of Hela/DDP apoptosis. Our results suggest a novel mechanism by which upregulated expression of AKT3 in cervical cancer may lead to resistance to cisplatin. | Authentic |
Text : Evidence suggests that the long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is upregulated in cancer tissues, and its elevated expression is associated with hyperproliferation. However, the underlying mechanisms regarding the role of MALAT1 in retinoblastoma (RB) remain unclear. This study aimed to explore the functional role of MALAT1 in RB by targeting miR-124. The results showed that the expression of MALAT1 was significantly higher in the Y79 cell line than in the ARPE-19 cell line (p < 0.01). Moreover, MALAT1 silence inhibited cell viability, migration, and invasion and promoted apoptosis in Y79 cells (p < 0.05, p < 0.01, or p < 0.001). miR-124 was upregulated by MALAT1 silence and hence was identified as a target of MALAT1 (p < 0.05 or p < 0.001). In addition, miR-124 suppression inhibited cell apoptosis and remarkably abolished the inhibitory effects of MALAT1 silence on cell viability, migration, and invasion (p < 0.05, p < 0.01, or p < 0.001). In addition, Slug was a target of miR-124 and regulated cell viability, migration, invasion, and apoptosis in Y79 cells (p < 0.05, p < 0.01, or p < 0.001). Further, Slug silence abolished miR-124 suppression-induced inactivation of the ERK/MAPK and Wnt/β-catenin pathways. Taken together, our data highlight the pivotal role of MALAT1 in RB. Moreover, the present study elucidated the MALAT1-miR-124-ERK/MAPK and Wnt/β-catenin signaling pathways in RB, which might provide a new approach for the treatment of RB. | Counterfeit |
Text : Tumor suppressor gene PTEN is frequently mutated in a wide variety of cancers. However, the downstream targets or signal transduction pathways of PTEN remain not fully understood. By analyzing Pten-null mouse embryonic fibroblasts (MEFs) cell lines and their isogenic counterparts, we showed that loss of PTEN led to increased cyclooxygenase2 (COX2) expression in an AKT-independent manner. Moreover, we demonstrated that PTEN deficiency promotes the transcription of COX2 via upregulation of the transcription factor Krüppel-like factor 5 (KLF5). Knocked down the expression of COX2 suppressed proliferation, migration and tumoral growth of Pten-null cells. Further experiments revealed that COX2 enhanced Pten-null MEFs growth and migration through upregulation of NADPH oxidase 4 (NOX4). In addition, MK-2206, a specific inhibitor of AKT, in combination with celecoxib, a COX2 inhibitor, strongly inhibited Pten-deficient cell growth. We concluded that KLF5/COX2/NOX4 signaling pathway is critical for cell growth and migration caused by the loss of PTEN, and the combination of MK-2206 and celecoxib may be an effective new approach to treating PTEN deficiency related tumors. | Authentic |
Text : BCR-ABL kinase domain (KD) mutations are well known for causing resistance against tyrosine kinase inhibitors (TKIs) and disease progression in chronic myeloid leukemia (CML). In recent years, compound BCR-ABL mutations have emerged as a new threat to CML patients by causing higher degrees of resistance involving multiple TKIs, including ponatinib. However, there are limited reports about association of compound BCR-ABL mutations with disease progression in imatinib (IM) sensitive CML patients. Therefore, we investigated presence of ABL-KD mutations in chronic phase (n = 41), late chronic phase (n = 33) and accelerated phase (n = 16) imatinib responders. Direct sequencing analysis was used for this purpose. Eleven patients (12.22%) in late-CP CML were detected having total 24 types of point mutations, out of which 8 (72.72%) harbored compound mutated sites. SH2 contact site mutations were dominant in our study cohort, with E355G (3.33%) being the most prevalent. Five patients (45%) all having compound mutated sites, progressed to advanced phases of disease during follow up studies. Two novel silent mutations G208G and E292E/E were detected in combination with other mutants, indicating limited tolerance for BCR-ABL1 kinase domain for missense mutations. However, no patient in early CP of disease manifested mutated ABL-KD. Occurrence of mutations was found associated with elevated platelet count (p = 0.037) and patients of male sex (p = 0.049). The median overall survival and event free survival of CML patients (n = 90) was 6.98 and 5.8 y respectively. The compound missense mutations in BCR-ABL kinase domain responsible to elicit disease progression, drug resistance or disease relapse in CML, can be present in yet Imatinib sensitive patients. Disease progression observed here, emphasizes the need of ABL-KD mutation screening in late chronic phase CML patients for improved clinical management of disease. | Authentic |
Text : Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death. HBV infection is an important risk factor for the tumorigenesis of HCC, given that the inflammatory environment is closely related to morbidity and prognosis. Consequently, it is of urgent importance to explore the immunogenomic landscape to supplement the prognosis of HCC. The expression profiles of immune-related genes (IRGs) were integrated with 377 HCC patients to generate differentially expressed IRGs based on the Cancer Genome Atlas (TCGA) dataset. These IRGs were evaluated and assessed in terms of their diagnostic and prognostic values. A total of 32 differentially expressed immune-related genes resulted as significantly correlated with the overall survival of HCC patients. The Gene Ontology functional enrichment analysis revealed that these genes were actively involved in cytokine-cytokine receptor interaction. A prognostic signature based on IRGs (HSPA4, PSME3, PSMD14, FABP6, ISG20L2, TRAF3, NDRG1, NRAS, CSPG5, and IL17D) stratified patients into high-risk versus low-risk groups in terms of overall survival and remained as an independent prognostic factor in multivariate analyses after adjusting for clinical and pathologic factors. Several IRGs (HSPA4, PSME3, PSMD14, FABP6, ISG20L2, TRAF3, NDRG1, NRAS, CSPG5, and IL17D) of clinical significance were screened in the present study, revealing that the proposed clinical-immune signature is a promising risk score for predicting the prognosis of HCC. | Authentic |
Text : Increasing evidence suggests that glutathione peroxidase 2 (GPX2) plays important roles in the tumorigenesis and progression of various human cancers, such as colorectal carcinomas and lung adenocarcinomas. However, the role of GPX2 in cervical cancer is unclear. In this study, we identified the role of GPX2 in cervical cancer tissues and cell lines. The basal mRNA and protein expression of GPX2 in cervical cancer cells and a series of key molecules in the epithelial to mesenchymal transition (EMT) and WNT/β-catenin pathways were examined via real time fluorescence quantitative PCR (qRT-PCR) and Western blot assays. The biological phenotype of the cervical cancer cell lines was detected by the cloning formation and transwell assays, and intracellular reactive oxygen species (ROS) levels were detected by flow cytometry. Finally, the GPX2 expression level in 100 clinical cervical tissues was examined by immunohistochemistry. We found that GPX2 was highly expressed in cervical cancer tissues compared to normal individuals and promoted the proliferation and metastasis of cervical cancer cells, and this promotion correlated with the activation of EMT and WNT/β-catenin signaling in vitro. GPX2 was determined to reduce apoptotic damage by reducing hydroperoxides. According to the characteristics and verification of GPX2, this series of phenotypes is clearly related to oxidative stress in cells. Furthermore, we verified that GPX2 was highly expressed in cervical cancer tissues and promoted the metastasis of cervical cancer. In summary, we found that GPX2 was highly expressed in cervical cancer cells and promoted the proliferation and metastasis of cervical cancer by affecting oxidative stress. Our study provides a new target for the clinical treatment of cervical cancer. | Authentic |
Text : The incidence of cancer is growing worldwide, and it is becoming the most common cause of death. Long non-coding RNAs (lncRNAs) are a group of RNA transcripts with a length larger than 200 nucleotides that cannot encode proteins or peptides. LncRNAs regulate different biological functions by controlling gene expressions at transcriptional, translational, and post-translational levels. Non-coding RNA activated by DNA damage (NORAD) is a highly conserved lncRNA necessary for genome stability. LncRNA NORAD is dysregulated in various types of cancers. This biomarker has been involved in numerous processes associated with carcinogeneses, such as cell proliferation, apoptosis, invasion, and metastasis. In this paper, we reviewed the role of lncRNA NORAD and its biological functions in various human cancers to provide future research insights. | Authentic |
Text : Valid evidence has demonstrated that microRNAs have critical functions in cancer genesis and tumor progression. In the present study, aberrant expression of microRNA-149 (miR-149) was confirmed in non-small cell lung cancer (NSCLC) tissues. Low expression of miR-149 was associated with malignant clinical features and poor survival. Gain- and loss-of-function experiments demonstrated that miR-149 inhibited NSCLC tumor growth and metastasis in vitro and in vivo. Furthermore, oncogenic transcription factor FOXM1 was confirmed as a direct target of miR-149 in NSCLC. Cyclin D1 and MMP2 served as downstream targets of FOXM1 and were also inhibited by miR-149. In summary, the present study indicated that downregulation of miR-149 in NSCLC predicted poor clinical outcomes. miR-149 suppresses tumor growth and metastasis in NSCLC by inhibiting the FOXM1/cyclin D1/MMP2 signaling pathway. | Authentic |
Text : MicroRNAs (miRNAs) play an important role in carcinogenesis. miR-218 is one of the most known miRNAs and has been demonstrated to inhibit progression in gastric cancer. However, the underlying molecular mechanism is not established. In this study, qRT-PCR and Western blot indicated that miR-218 was downregulated in gastric cancer cell lines SGC7901 and BGC823 compared to that in normal gastric epithelial cell line GES-1. MTT and wound scratch assays suggested that overexpression of miR-218 markedly suppressed cell proliferation, migration, and EMT of gastric cancer cells. Furthermore, we proved that WASF3 was a direct target of miR-218 by luciferase reporter assay, and restoration of WASF3 expression impairs miR-218-induced inhibition of proliferation, migration, and EMT in gastric cancer cells SGC7901. In summary, our results demonstrated that miR-218 functions as one of the tumor-suppressive miRNAs and inhibits gastric cancer tumorigenesis by targeting WASF3. miR-218 may serve as a potential therapeutic target for the treatment of gastric cancer. | Authentic |
Text : Hepatocellular carcinoma (HCC), as one of the commonest cancers globally, is a primary malignancy in human liver with a characteristic of high mortality rate. Long noncoding RNAs (lncRNAs) are confirmed to be implicated with multiple cancers including HCC. LncRNA FAM83A-AS1 has also been validated as an oncogene in lung cancer, but its mechanism in HCC is poorly understood. Our research is intended to investigate the underlying mechanism of FAM83A-AS1 in HCC. In the present study, we found the abundantly increased expression level of FAM83A-AS1 in HCC tissues and cells. FAM83A-AS1 inhibition hampered cell proliferation, migration and elevated cell apoptosis in HCC. Moreover, FAM83A-AS1 could positively regulate FAM83A, and FAM83A could also promote the progression of HCC. In addition, FAM83A-AS1 and FAM83A were both verified to bind with NOP58, and FAM83A-AS1 enhanced the mRNA stability of FAM83A by binding with NOP58. In rescue assays, the suppressed influence of down-regulated FAM83A-AS1#1 on cell proliferation, migration as well as the accelerated influence of FAM83A-AS1#1 knockdown on cell apoptosis could be partially recovered by overexpression of FAM83A. In conclusion, FAM83A-AS1 facilitated HCC progression by binding with NOP58 to enhance the stability of FAM83A. These findings offer a novel biological insight into HCC treatment. | Authentic |
Text : Diabetic retinopathy (DR) is a common complication of diabetes mellitus, which is a major reason of blindness. Baicalin (BAI) is a flavonoid extracted from Scutellaria baicalensis, whose pharmacological characterizes have been widely reported in various diseases. However, it remains unclear the effect of BAI on DR. The study aimed to confirm the protective effect of BAI on DR. ARPE-19 cells and HRMECs were exposed to the high glucose (HG) environment to construct a cell injury model. After treatment with HG and BAI, cell viability, apoptosis, inflammatory cytokines and ROS generations were determined in ARPE-19 cells and HRMECs. Subsequently, microRNA-145 (miR-145) inhibitor and its negative control were transfected into ARPE-19 cells, and the regulatory effects on HG-and BAI-co-treated cells were detected. NF-κB and p38MAPK signaling pathways were finally examined to state the underling mechanisms. HG treatment significantly induced ARPE-19 cells and HRMECs injury in vitro. BAI significantly promoted cell proliferation, reduced apoptosis, as well as inhibited the release of IL-1β, IL-6, IL-8 and ROS level in HG-injured ARPE-19 cells and HRMECs. Additionally, the expression level of miR-145 was up-regulated in HG-and BAI-co-treated cells. More importantly, miR-145 inhibition reversed the protective effect of BAI on HG-injured ARPE-19 cells. Besides, we observed that BAI inhibited the activations of NF-κB and p38MAPK pathways by up-regulating miR-145. Results demonstrated that BAI exhibited the protective effect against HG-induced cell injury by up-regulation of miR-145. | Counterfeit |
Text : Chronic rhinosinusitis (CRS) is featured with chronic symptoms of inflammation or infection in the nasal and sinus tissues. MicroRNAs (miRNAs/miRs), such as dysregulated expression of miR-125b and miR-26a, has been previously demonstrated to be related to CRS. The present study is intended to define the role of miR-335-5p in inflammation and the related mechanism in a mouse model of CRS. The differentially expressed genes associated with CRS were screened by microarray analysis. The targeting relationship between miR-335-5p and TPX2 was analyzed by target prediction program and dual luciferase reporter gene assay. The mouse model of CRS was established, and mice were introduced with miR-335-5p mimics, miR-335-5p inhibitors, or siRNA against TPX2 to explore the regulatory functions of miR-335-5p. The regulatory effect of miR-335-5p on inflammation with the involvement of the AKT signaling pathway was also analyzed with the expression of inflammatory cytokines and AKT signaling pathway-related factors measured. It was indicated that miR-335-5p regulated the TPX2 gene-mediated AKT signaling pathway. TPX2 was identified as a target gene of miR-335-5p, and miR-335-5p elevation inhibited the activation of the AKT signaling pathway. In mice with CRS, up-regulation of miR-335-5p or silence of TPX2 inhibited the inflammation, as evidenced by decreased levels of TNF-α, IL-6 and IL-8, and higher levels of GSK3β and IL-10. Collectively, miR-335-5p inhibits the activation of AKT signaling pathway by negatively mediating TPX2, which may confer anti-inflammatory protection in CRS. | Counterfeit |
Text : Cervical cancer, the only gynecological malignancy for which a clear pathogeny has been established, has an incidence rate only second to breast cancer. In our study, we aim to investigate the clinical effect of laparoscopic radical surgery combined with neoadjuvant chemotherapy in treating cervical cancer and its influence on postoperative complications and adverse reaction rates. Cervical cancer patients admitted to our hospital from August 2018 to May 2020 were retrospectively analyzed as the research object and divided into the control group and the experimental group by the draw method, with 50 cases in each group. The laparoscopic radical surgery was performed on the control group, and the laparoscopic radical surgery combined with neoadjuvant chemotherapy was performed on the experimental group to compare their effective rates, adverse reaction rates, postoperative complication rates, expression levels of serum tumor necrosis factor-α (TNF-α) and soluble interleukin-2 receptor (SIL-2R) inside the body before surgery and at one week after surgery, quality of life (QLI) scores, and Mental Status Scale in Nonpsychiatric Settings (MSSNS) scores. Compared with the control group, the experimental group obtained significantly higher effective rate and QLI scores (P < 0.05) and significantly lower adverse reaction rates, postoperative complication rates, expression levels of serum TNF-α and SIL-2R inside the body at one week after surgery, and MSSNS scores (P < 0.05), with statistical differences; before surgery, the TNF-α and SIL-2R expression levels of the two groups were not significantly different (P > 0.05), but the levels at one week after surgery were significantly lower than those before, indicating statistical significance (P < 0.05). The clinical effect of laparoscopic radical surgery combined with neoadjuvant chemotherapy can obviously improve the effective rate of cervical cancer patients and lower the incidence rates of postoperative complications and adverse reactions. | Authentic |
Text : Recently, the biggest challenge in the treatment of breast cancer is the metastasis of breast cancer cells. Multiple myeloma SET protein (MMSET), a histone lysine methyltransferase, overexpressed in various human cancers, was reported to be associated with carcinogenesis of human cancers. Expression of MMSET in breast cancer cell lines and tissues was quantified by real-time PCR and Western blotting. Immunohistochemistry was employed to analyze MMSET expression in 163 clinicopathologically characterized breast cancer cases. Cell functional assays such as MTT assay, colony formation, BrdU assay, flow cytometry, wound healing, Transwell assay, and 3D culture were used to investigate the effect of MMSET in the development and metastasis of human breast cancer. Effects of MMSET on Wnt/β-catenin signaling pathway were further studied by using Western blotting analysis. Our results showed that MMSET expression was markedly overexpressed in breast cancer cells and clinical specimens and was significantly correlated with patients' clinicopatho-logic characteristics and prognosis. Moreover, silencing endogenous MMSET significantly inhibited the proliferation, migration, and metastasis of breast cancer cells through inhibiting the Wnt/β-catenin pathway. This study found that the downregulated expression of MMSET impaired proliferation and metastasis of human breast cancer through inhibiting Wnt/β-catenin signaling pathway. Notably, our results indicated that MMSET could be a useful biomarker for the prognosis of breast cancer. | Authentic |
Text : Hepatocellular carcinoma (HCC) is the leading cause of tumor-related death worldwide due to high morbidity and mortality, yet lacking effective biomarkers and therapies. Circular RNAs (circRNAs) are a group of non-coding RNAs that regulate gene expression through interacting with miRNAs, implicating in the tumorigenesis and progression. A novel circRNA, circTP63, was reported to be an oncogene in HCC. However, its role in HCC remains unclear. qRT-PCR was used to assess the mRNA levels of CircTP63 in 90 pairs of tumor and adjacent normal tissues from HCC patients, one human normal hepatic epithelial cell line and HCC cell lines. CCK-8, colony formation, transwell, and flow cytometry assays were performed to detect the cellular function of circTP63/miR-155-5p/ZBTB18 in HCC cells. HCC xenograft mice models were established to assess the in vivo effect of circTP63. Bioinformatic analysis, RNA pull-down and luciferase assays were used to determine the interaction among circTP63/miR-155-5p/ZBTB18. circTP63 was significantly upregulated in HCC tissues and cell lines. High circTP63 expression is closely associated with the tumor stages, lymph node metastasis, and poor prognosis of HCC patients. Functionally, knockdown of circTP63 inhibited cell proliferation, migration, invasion, and promoted cell apoptosis of HCC. Meanwhile, overexpression of circTP63 enhanced HCC progression. Mechanically, circTP63 was a sponge of miR-155-5p to facilitate the ZBTB18 expression, and the ZBTB18 expression in HCC tissues was negatively associated with the survival rate of HCC patients. Furthermore, rescued assays revealed that the reduced tumor-promoting effect on HCC cells induced by knockdown of circTP63 can be reversed by miR-155-5p inhibitor or ZBTB18 overexpression. Our data highlight a critical circTP63-miR-155-5p-ZBTB18 regulatory network involved in the HCC progression, gaining mechanistic insights into the function of circRNAs in HCC progression, and providing effective biomarkers and therapeutic targets for HCC treatment. | Authentic |
Text : Tripartite motif containing 37 (TRIM37), a member of the tripartite motif (TRIM) family, has been involved in the development and progression of several tumors. However, its role in non-small cell lung cancer (NSCLC) is still unclear. Therefore, the aim of this study was to investigate the expression pattern and role of TRIM37 in NSCLC. Our results showed that TRIM37 was highly expressed in human NSCLC cell lines. Knockdown of TRIM37 obviously inhibited the proliferation in vitro and xenografted tumor growth in vivo. Furthermore, knockdown of TRIM37 suppressed NSCLC cell migration and invasion by inhibiting the epithelial-mesenchymal transition (EMT) phenotype. Lastly, knockdown of TRIM37 greatly down-regulated the protein expression levels of β-catenin, cyclinD1 and c-myc in A549 cells. In conclusion, the present study revealed that TRIM37 plays an important role in the development and progression of NSCLC. Thus, TRIM37 may act a potential therapeutic target for treating NSCLC. | Authentic |
Text : Ovarian cancer is the most lethal gynecologic malignancy worldwide with extremely poor patient prognosis. Elucidation of the detailed mechanisms of action of drugs targeting this cancer type is necessary to optimize treatment efficacy. Epothilones, a new class of microtubule-stabilizing anticancer drugs, show strong cytotoxic properties in vitro and in vivo and are additionally effective in taxane-resistant cells. In this report, we focus on inhibitors of microtubule depolymerization, taxanes, and the novel antimicrotubule agents, epothilones. Current knowledge regarding the effects of epothilone B on ovarian tumor cell metabolism is reviewed, along with recent advances in therapeutic strategies, such as novel agents and biologic drug combinations containing epothilone that target aberrant pathways in ovarian cancer. | Authentic |
Text : The objective of this study is to explore the role of MALAT1 as a molecular indicator in predicting the recurrence, metastasis, and prognosis of gallbladder cancer (GBC) and its effect on the proliferation, invasion, migration, and apoptosis of GBC cells in vitro. GBC tissues and adjacent normal tissues were collected from 102 patients. MALAT1 short hairpin RNA (shRNA) plasmids were first constructed to transfect the GBC-SD cells. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was applied to detect MALAT1 expression. CCK-8 assay, flow cytometry, and Transwell assay were applied to testify the cell proliferation, cell cycle, apoptosis, invasion, and migration. A receiver operating characteristic (ROC) curve was used to evaluate the values of MALAT1 in GBC recurrence, metastasis, and prognosis. COX regression analysis was applied to analyze the independent influencing factors of GBC patients' survival status. ROC curve results showed that the MALAT1 expression could be a predictor of the GBC recurrence, metastasis, and prognosis. According to the COX regression analysis, MALAT1 expression, tumor size, and TNM stage were independent influencing factors of GBC patients' survival condition. Compared with the GBC-SD cells transfected with empty plasmids, those transfected with MALAT1 shRNA plasmids showed higher apoptosis rates, weakened proliferation, migration, and invasion. In conclusion, our findings demonstrate that lncRNA MALAT1 can be considered as an indicator for evaluating the recurrence, metastasis, and prognosis of GBC patients. We also demonstrate how the overexpression of MALAT1 confers an oncogenic function in GBC. | Authentic |
Text : Low effectiveness of anti-melanoma therapies makes it necessary to search for new drugs that could improve or replace the standard chemotherapy. Fluoroquinolones are a group of synthetic antibiotics, used in the treatment of wide range of bacterial infections. Moreover, this class of antibiotics has shown promising anti-tumor activity in several cancer cell lines. The aim of this study was to examine the effect of ciprofloxacin on cell viability, apoptosis and cell cycle distribution in COLO829 melanoma cells. Cell viability was evaluated by the WST-1 assay. Cell cycle distribution and apoptosis in cells exposed to ciprofloxacin was analyzed by the use of fluorescence image cytometer NucleoCounter NC-3000. Ciprofloxacin decreased the cell viability in a dose- and time-dependent manner. For COLO829 cells treated with ciprofloxacin for 24 h, 48 h and 72 h the values of IC50 were found to be 0.74 mM, 0.17 mM and 0.10 mM, respectively. The oligonucleosomal DNA fragmentation was observed when the cells were exposed to ciprofloxacin in concentration of 1.0 mM for 48 h and 72 h. At lower ciprofloxacin concentrations (0.01 mM and 0.1 mM) cells were arrested in S-phase suggesting a mechanism related to topoisomerase II inhibition. Moreover, it was demonstrated that ciprofloxacin induced apoptosis as a result of mitochondrial membrane breakdown. The obtained results for COLO829 melanoma cells were compared with data for normal dark pigmented melanocytes and the use of ciprofloxacin as a potential anticancer drug for the treatment of melanoma in vivo was considered. | Authentic |
Text : Esophageal cancer is one of the most common cancers in the world and esophageal squamous cell carcinoma is one of the two main types in esophageal cancer. MicroRNA is a small non-coding RNA molecule functions in many different cancers including esophageal cancer. We found miR-502 was up-regulated in esophageal tissues, which indicated miRNA-502 may play important roles in esophageal cancer. In this study, we used esophageal cancer cell line TE1 as an in vitro model for investigating the role of miR-502 in promoting the proliferation of the cancer cells. We found that overexpressing miR-502 in TE1 cells promoted the proliferation and inhibited the apoptosis induced by dox. Down-regulating miR-502 made the opposite phenomenon. Furthermore, western blot showed that miR-502 enhanced the phosphorylation levels of AKT pathways, which may be the mechanism of the overgrowth for esophageal cancer cell. Our data provide the evidence of a role for miR-502 in the regulation the proliferation of esophageal cancer cell through promoting the phosphorylation of AKT signaling. Due to its ability to promote the overgrowth of esophageal cancer cell, miR-502 may be a novel target for esophageal cancer therapeutic. | Authentic |
Text : Extensive research has revealed that microRNAs (miRNAs) play a principle role in cancer, and miRNAs associated with specific cancers have also been identified. The role of microRNA (miR)-302b-5p, which is one of the miRNAs reported in association with cancer, in hepatocellular carcinoma (HCC) is still unclear. Thus, the present study aimed to reveal the expression and potential molecule mechanism of miR-302b-5p in HCC. An extensive meta-analysis of data from real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR), Gene Expression Omnibus and ArrayExpress microarrays was used to determine the expression of miR-302b-5p in HCC tissue samples and non-cancerous liver tissue samples. The sensitivity and specificity of miR-302b-5p as an indicator of HCC was estimated by plotting the receiver operating characteristic (ROC) and summarized ROC (sROC). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were employed to unravel the molecular mechanisms and biological functions of miR-302b-5p in HCC. Further, the putative target genes of miR-302b-5p were harvested based on the predicted genes and differentially expressed genes in HCC. Finally, the protein-protein interaction (PPI) network was built to determine the hub genes. According to the RT-qPCR results, the expression of miR-302b-5p was pronouncedly decreased in 39 HCC tissue samples as compared to 39 non-cancerous liver tissue samples. The standard mean difference (SMD) values of all the samples used in the meta-analysis also indicated lower miR-302b-5p expression in the 558 HCC tissue samples than in the 286 non-cancerous liver tissue samples. ROC and sROC analyses showed that miR-302b-5p had good specificity and sensitivity for distinguishing HCC tissue from non-cancerous liver tissue. Bioinformatics analyses identified 227 putative genes, and these genes were evidently enriched in the processes of organelle fission, chromosome and chromatin binding and were centralized in a "lysosome" pathway. The PPI network indicated that DNA topoisomerase II alpha (TOP2 A) was the most prominent hub gene of miR-302b-5p in HCC. Interestingly, according to the TCGA and Genotype-Tissue Expression databases, the mRNA and protein expression of TOP2 A were both elevated in HCC tissue samples as compared to non-cancerous liver tissue samples, and the overall survival and disease-free survival revealed that a high level of TOP2 A might reflect poor HCC outcome. Our findings indicate that miR-302b-5p might suppress HCC progression, and TOP2 A might be a potential target of miR-302b-5p in HCC. However, in-depth in vivo and in vitro experiments are required to verify these findings and explore the mechanisms involved. | Authentic |
Text : Novel, less toxic, cost-effective and safe therapeutic strategies are needed to improve treatment of chronic lymphocytic leukemia (CLL). Ascorbic acid (AA, vitamin C) has shown a potential anti-cancer therapeutic activity in several cancers. However, the anti-cancer effects of ascorbic acid on CLL B-cells have not been extensively studied. We aimed in this study to evaluate the in vitro therapeutic activity using clinically relevant conditions. Primary CLL B-cells and two CLL cell lines were exposed to a dose that is clinically achievable by AA oral administration (250 μM), and cell death and potential mechanisms were assessed. The role of the protective CLL microenvironment was studied. Synergistic interaction between AA and CLL approved drugs (Ibrutinib, Idelalisib and Venetoclax) was also evaluated. Ascorbic acid is cytotoxic for CLL B-cells at low dose (250 μM) but spares healthy B-cells. Ascorbic-acid-induced cytotoxicity involved pro-oxidant damage through the generation of reactive oxygen species in the extracellular media and in CLL cells, and induced caspase-dependent apoptosis. We also found that AA treatment overcame the supportive survival effect provided by microenvironment including bone marrow mesenchymal stem cells, T-cell cues (CD40L + IL-4), cytokines and hypoxia. Our data suggest that resistance to AA could be mediated by the expression of the enzyme catalase in some CLL samples and by the glucose metabolite pyruvate. We also demonstrated that AA synergistically potentiates the cytotoxicity of targeted therapies used in or being developed for CLL. These preclinical results point to AA as an adjuvant therapy with potential to further improve CLL treatments in combination with targeted therapies. | Authentic |
Text : In information science, modern and advanced computational methods and tools are often used to build predictive models for time-to-event data analysis. Such predictive models based on previously collected data from patients can support decision-making and prediction of clinical data. Therefore, a new simple and flexible modified log-logistic model is presented in this paper. Then, some basic statistical and reliability properties are discussed. Also, a graphical method for determining the data from the log-logistic or the proposed modified model is presented. Some methods are applied to estimate the parameters of the presented model. A simulation study is conducted to investigate the consistency and behavior of the discussed estimators. Finally, the model is fitted to two data sets and compared with some other candidates. | Authentic |
Text : Although many factors determine the prognosis of papillary thyroid carcinoma (PTC), cervical lymph node metastasis (CLNM) is one of the most terrible factors. In view of this, this study aimed to build a CLNM prediction model for papillary thyroid microcarcinoma (PTMC) with the help of machine learning algorithm. We retrospectively analyzed 387 PTMC patients hospitalized in the Department of Medical Oncology, Enshi Tujia and Miao Autonomous Prefecture Central Hospital from January 1, 2015, to January 31, 2022. Based on supervised learning algorithms, namely random forest classifier (RFC), artificial neural network(ANN), support vector machine(SVM), decision tree(DT), and extreme gradient boosting gradient(XGboost) algorithm, the LNM prediction model was constructed, and the prediction efficiency of ML-based model was evaluated via receiver operating characteristic curve(ROC) and decision curve analysis(DCA). Finally, a total of 24 baseline variables were included in the supervised learning algorithm. According to the iterative analysis results, the pulsatility index(PI), resistance index(RI), peak systolic blood flow velocity(PSBV), systolic acceleration time(SAT), and shear wave elastography elastic index(SWEEI), such as average value(Emean), maximum value(Emax), and minimum value(Emix) were candidate predictors. Among the five supervised learning models, RFC had the strongest prediction efficiency with area under curve(AUC) of 0.889 (95% CI: 0.838-0.940) and 0.878 (95% CI: 0.821-0.935) in the training set and testing set, respectively. While ANN, DT, SVM and XGboost had prediction efficiency between 0.767 (95% CI: 0.716-0.818) and 0.854 (95% CI: 0.803-0.905) in the training set, and ranged from 0.762 (95% CI: 0.705-0.819) to 0.861 (95% CI: 0.804-0.918) in the testing set. We have successfully constructed an ML-based prediction model, which can accurately classify the LNM risk of patients with PTMC. In particular, the RFC model can help tailor clinical decisions of treatment and surveillance. | Authentic |
Text : Lung cancer is considered as the most prevalent form of cancer and it is found to be frequent cause of cancer related death. Even though, approved molecular targeted therapies other than chemotherapy are currently unavailable, the mechanism of pathogenesis in lung cancer remains still unclear. Transcription factors (TFs) play a critical role in cancer cell processes, such as cell proliferation, apoptosis, migration, and regulate gene expression. Thus, the identification and characterization of transcription factors involved in lung cancer would provide valuable information for further elucidation of the mechanism(s) underlying pathogenesis and the identification of potential therapeutic target types, which are critical for the development of therapeutic strategies. Through an extensive literature survey, we have identified 349 transcription factors noted for their strong involvement in lung cancer. Database of Transcription Factors in Lung Cancer (DBTFLC) was constructed as a data repository and analytical platform for systematic collection, curation of TFs and their interacting partners. The database includes all pertinent information such as lung cancer related TFs, chromosomal location, family, lung cancer type, references, TF-TF interaction(s), and TF-target gene interaction(s); thus, it could serve as a valuable resource for therapeutic studies in lung cancer. The database is freely available at http://www.vit.ac.in/files/database/Home.php. | Authentic |
Text : Non-small cell lung cancer (NSCLC) is the main histological subtype of lung cancer, which is the leading cause of cancer death. It is unclear whether the improved survival seen at high-volume centers applies to the general population and, more importantly, whether the improvement in lung cancer survival was just a consequence of improved screening work. Data from the Surveillance, Epidemiology, and End Results (SEER) registry was used to identify 405,580 patients with NSCLC diagnosed from 1988 to 2008. The patients were divided into four groups according to the year of diagnosis. Trends of clinical characteristics were analyzed to reflect the progress of screening work. Five-year relative survivals in various subgroups were compared. The results indicated that proportion of aged, advanced, and non-surgical patients increased, whereas patients with lymph node metastasis and high histology grade decreased. Improvements in all stages of NSCLC patients were demonstrated, with relatively more significant gains for patients with localized and regional disease. After potentially curative surgical resection, remarkable improvements were observed in both cohorts with time (surgical: 52.00%-63.00%; non-surgical: 6.10%-13.50%). Specifically, patients who underwent pneumonectomy, lobectomy/bilobectomy, and partial/wedge/segmental resection all presented better survival rates. Our SEER analysis demonstrated improvements among patients in all stages of NSCLC that were deemed attributable to improved therapy and medical care for NSCLC rather than improved screening work. | Authentic |
Text : Psychological stress has been associated with transient global amnesia (TGA). Whether a cancer diagnosis, a severely stressful life event, is associated with subsequent risk of TGA has not been studied. Based on the Swedish Cancer Register and Patient Register, we conducted a prospective cohort study including 5,365,608 Swedes at age 30 and above during 2001-2009 to examine the relative risk of TGA among cancer patients, as compared to cancer-free individuals. Incidence rate ratios (IRRs) and their 95% confidence intervals (CIs) derived from Poisson regression were used as estimates of the association between cancer diagnosis and the risk of TGA. During the study 322,558 individuals (6.01%) received a first diagnosis of cancer. We identified 210 cases of TGA among the cancer patients (incidence rate, 0.22 per 1000 person-years) and 4,887 TGA cases among the cancer-free individuals (incidence rate, 0.12 per 1000 person-years). Overall, after adjustment for age, sex, calendar year, socioeconomic status, education and civil status, cancer patients had no increased risk of TGA than the cancer-free individuals (IRR, 0.99; 95% CI, 0.86-1.13). The IRRs did not differ over time since cancer diagnosis or across individual cancer types. The null association was neither modified by sex, calendar period or age. Our study did not provide support for the hypothesis that patients with a new diagnosis of cancer display a higher risk of TGA than cancer-free individuals. | Authentic |
Text : Recently, the role of long noncoding RNA (lncRNAs) in tumor progression has caught many attentions. In this research, lncRNA AFAP1-AS1 was studied to identify how it functioned in the progression of prostate cancer. LncRNA AFAP1-AS1 expression was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) in both prostate cancer cells and tissue samples. In addition, to identify the function of AFAP1-AS1 on prostate cancer in vitro, cell proliferation, transwell assay, and Matrigel assay were conducted. Furthermore, by performing qRT-PCR and Western blot assay, the underlying mechanism was explored. The expression level of AFAP1-AS1 was significantly higher in prostate cancer samples than that in corresponding ones. Additionally, the cell proliferation, migration, and invasion capacities were inhibited after AFAP1-AS1 was knocked down in prostate cancer cells. Moreover, the mRNA and protein expressions of RBM5 were upregulated after AFAP1-AS1 was knocked down. Furthermore, the RBM5 expression level was negatively related to AFAP1-AS1 expression level in prostate cancer samples. AFAP1-AS1 acts as an oncogene in prostate cancer by enhancing cell metastasis and proliferation via suppressing RBM5, which might be a novel therapeutic strategy in treatment for prostate cancer. | Counterfeit |
Text : We aimed to investigate the significant role of long noncoding RNA X inactive specific transcript (XIST) in regulating tumor metastasis in colorectal cancer (CRC), as well as its possible mechanism. Expression of lncRNA XIST in CRC tissues and CRC cells was detected. CRC cells were transfected with pc-XIST, blank control si-XIST, or si-control, and then the effects of lncRNA XIST on CRC cell migration and invasion were investigated, along with the interaction between lncRNA XIST and miR-137. lncRNA XIST was upregulated in CRC tissues. Compared with HT29 cells that had low metastatic potential, XIST was markedly more highly expressed in LoVo cells that had a higher metastatic potential. Overexpression of XIST promoted the migratory and invasive potential of HT29 cells, while knockdown of XIST inhibited the migratory and invasive potential of LoVo cells. Moreover, epithelial-mesenchymal transition (EMT) markers, including E-cadherin, N-cadherin, and vimentin, exhibited corresponding expression changes. In addition, miR-137 was inhibited by XIST, and inhibition of miR-137 could reverse the effects of knockdown of XIST on the migratory and invasive potential of LoVo cells. Furthermore, enhancer of zeste homolog 2 (EZH2) was confirmed as a target of miR-137. Our data reveal that lncRNA XIST may promote tumor metastasis in CRC possibly through regulating the miR-137-EZH2 axis. lncRNA XIST may serve as a prognostic indicator for CRC progression. | Authentic |
Text : Liver cancer is one of the most common and lethal cancers in human digestive system, which kills more than half a million people every year worldwide. This study aimed to investigate the effects of kaempferol, a flavonoid compound isolated from vegetables and fruits, on hepatic cancer HepG2 cell proliferation, migration, invasion, and apoptosis, as well as microRNA-21 (miR-21) expression. Cell viability was detected using cell counting kit-8 (CCK-8) assay. Cell proliferation was measured using 5-bromo-2'-deoxyuridine (BrdU) incorporation assay. Cell apoptosis was assessed using Guava Nexin assay. Cell migration and invasion were determined using two-chamber migration (invasion) assay. Cell transfection was used to change the expression of miR-21. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to analyze the expressions of miR-21 and phosphatase and tensin homologue (PTEN). Expression of key proteins involved in proliferation, apoptosis, migration, invasion, and phosphatidylinositol 3-kinase/protein kinase 3/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway were evaluated using western blotting. Results showed that kaempferol significantly inhibited HepG2 cell proliferation, migration, and invasion, and induced cell apoptosis. Kaempferol remarkably reduce the expression of miR-21 in HepG2 cells. Overexpression of miR-21 obviously reversed the effects of kaempferol on HepG2 cell proliferation, migration, invasion, and apoptosis. Moreover, miR-21 negatively regulated the expression of PTEN in HepG2 cells. Kaempferol enhanced the expression of PTEN and inactivated PI3K/AKT/mTOR signaling pathway in HepG2 cells. In conclusion, kaempferol inhibited proliferation, migration, and invasion of HepG2 cells by down-regulating miR-21 and up-regulating PTEN, as well as inactivating PI3K/AKT/mTOR signaling pathway. | Authentic |
Text : Histone methyltransferase enhancer of zeste homolog 2 (EZH2) has been reported to be associated with certain malignant phenotypes in cervical cancer. However, clinicopathological parameters and clinical outcomes of EZH2 in cervical cancer, particularly in cervical squamous cell carcinoma (CSCC) remain largely unknown. The retrospective cohort comprising of 117 consecutive patients with CSCC was incorporated into a tissue microarray which also included 23 paired normal tissues. Immunohistochemical analysis was performed to evaluate the correlation between EZH2 expression and clinicopathological implications. Aberrant overexpression of EZH2 was frequently observed in CSCCs as compared with adjacent normal tissues (P=0.0005). Expression of EZH2 is associated with poor tumor differentiation grade (P=0.020) and lymphovascular invasion (P=0.012). Univariate analysis revealed that the patients with CSCC whose tumors exhibited higher EZH2 levels had inferior overall survival (OS) compared to those whose tumors expressed lower EZH2 (log rank P=0.004). In the multivariate analysis, EZH2 expression was an independent predictor of OS (hazard ratio = 1.836, 95% confidence interval: 1.090-2.993, P=0.022). EZH2 overexpression is common in the development of CSCC and is a promising prognostic predictor for patients with CSCC. | Authentic |
Text : Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer in the world. To comprehensively investigate the utility of microRNAs (miRNAs) and protein-encoding transcripts (messenger RNAs [mRNAs]) in HCC as potential biomarkers for early detection and diagnosis, we exhaustively mined genomic data from three available omics datasets (GEO, Oncomine, and TCGA), analyzed the overlaps among gene expression studies from 920 hepatocellular carcinoma samples and 508 healthy (or adjacent normal) liver tissue samples available from six laboratories, and identified 178 differentially expressed genes (DEGs) associated with HCC. Paired with miRNA and lncRNA data, we identified 23 core genes that were targeted by nine differentially expressed miRNAs and 21 HCC-specific lncRNAs. We further demonstrated that alterations in these 23 genes were quite frequent, with five genes altered in over 5% of the population. Patients with high levels of YWHAZ, ENAH, and HMGN4 tended to have high-grade tumors and shorter overall survival, suggesting that these genes could be promising candidate biomarkers for disease and poor prognosis in patients with HCC. Our comprehensive mRNA, miRNA, and lncRNA omics analyses from multiple independent datasets identified robust molecules that may be used as biomarkers for early HCC detection and diagnosis. | Authentic |
Text : Interleukin-17A (IL-17A) plays a significant role in many inflammatory diseases and cancers. The aim of this study is to investigate the effect of IL-17A on the invasiveness of colorectal cancer. In the study, we found that IL-17A could promote the migration and invasion of colorectal cancer cells. Furthermore, after being treated with IL-17A, the expression and activity of matrix metalloproteinase 2 (MMP-2) and MMP-9 were upregulated. Moreover, the nuclear/overall fractions and DNA-binding activity of p65 and p50 were dramatically elevated by IL-17A. Pretreatment with a nuclear factor-κB (NF-κB) inhibitor (PDTC) or PI3K/AKT inhibitor (LY294002) was proven to abolish the promoting effect of IL-17A on the invasion ability of colorectal cancer cells and upregulation of MMP-2/9. In conclusion, our findings demonstrated that IL-17A could promote the invasion of colorectal cancer cells by activating the PI3K/AKT/NF-κB signaling pathway and subsequently upregulating the expression of MMP-2/9. Our results suggest that IL-17A could serve as a promising therapeutic target for colorectal cancer. | Authentic |
Text : Magnetic nanoparticles (MNPs), especially superparamagnetic iron oxide nanoparticles (SPIONs), have long been studied as contrast agents for magnetic resonance imaging (MRI). Owing to recent progress in synthesis and surface modification, many new avenues have opened for this class of biomaterials. Such nanoparticles are not merely tiny magnetic crystals, but potential platforms with large surface-to-volume ratios. By taking advantage of the well developed surface chemistry of MNPs, a wide range of functionalities, such as targeting, imaging, detection and therapeutic features, can be loaded onto their surfaces. This property makes magnetic nanoparticles excellent biomaterials for molecular detection of infectious agents and cancer. This short review thus discusses current advances on magnetic nanoparticles as molecular detection agents for infectious agents and cancer. | Authentic |
Text : Epidemiological evidence has shown that body mass index (BMI) can predict survival in several types of cancer. However, the role of BMI in extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is still unclear. This retrospective single-center study included 251 newly diagnosed patients to determine the prognostic value of BMI in ENKTL. Of these, 203 patients received chemoradiotherapy, 37 received chemotherapy alone, 8 received radiotherapy alone, and 3 received only best supportive care. With a median follow-up of 28 months, the estimated 3-year overall survival (OS) and progression-free survival (PFS) rates were 64.4% and 60.9%, respectively. The receiver-operating characteristic curve showed that 20.8 kg/m2 was the optimal cut-off of BMI to predict survival. BMI < 20.8 kg/m2 was associated with lower 3-year OS (52.8% vs. 72.9%, P = 0.001) and PFS (48.8% vs. 69.8%, P < 0.001) rates. Multivariate analysis indicated that BMI, performance status, lactate dehydrogenase (LDH) levels, chemotherapy, and radiotherapy were independent prognostic factors for OS. Furthermore, BMI, number of extranodal sites, performance status, LDH, and radiotherapy were predictive of PFS. These results suggest that BMI at the cut-off of 20.8 kg/m2 might be a prognostic factor in patients with ENKTL. | Authentic |
Text : Deregulation of microRNAs (miRNAs) has been widely reported in retinoblastoma (RB), and the aberrantly expressed miRNAs may serve as crucial epigenetic regulators in the occurrence and development of RB. Therefore, the identification of dysregulated miRNAs in RB may be useful for the development of effective targets for the therapy patients with this disease. miRNA (miR)‑485‑5p (miR‑485) is deregulated in multiple human cancer types and serves crucial roles in their progression and development. However, the expression pattern of miR‑485 and its role in RB have not been well investigated. In the present study, expression levels of miR‑485 in RB tissues and cell lines were measured using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The effects of miR‑485 overexpression on RB cell proliferation, apoptosis, migration and invasion were examined using Cell Counting Kit‑8 assay, flow cytometric analysis and in vitro migration and invasion assays, respectively. Xenograft tumor formation assay was utilized to determine the influence of miR‑485 on RB tumor growth in vivo. The mechanism responsible for the tumor‑suppressing roles of miR‑485 in RB progression was determined through a series of experiments, including bioinformatics prediction, luciferase reporter assay, RT‑qPCR, western blot analysis and rescue experiments. Herein, a marked downregulation of miR‑485 expression in human RB tissues and cell lines was observed. miR‑485 overexpression suppressed RB cell proliferation, induced cell apoptosis, attenuated cell migration and cell invasion in vitro, and restrained the growth of RB cells in vivo. Additionally, Wnt3a was revealed to be a direct target gene of miR‑485 in RB cells. Wnt3a was upregulated in human RB tissues, and its upregulation was inversely associated with miR‑485. Furthermore, the tumor suppressive roles of Wnt3a silencing were similar to those of miR‑485 overexpression in RB cells. In addition, restoration of Wnt3a expression partially reversed the tumor suppressor action of miR‑485 in RB cells. However, miR‑485 upregulation directly targeted Wnt3a to inhibit activation of the Wnt/β‑catenin signaling pathway in RB cells both in vitro and in vivo. Notably, these results demonstrated that the tumor‑suppressive roles of miR‑485 were at least partially mediated by Wnt3a in RB cells. Therefore, miR‑485 is a potential therapeutic target for treating patients with RB. | Counterfeit |
Text : Ovarian cancer is usually treated with transurethral resection or systemic chemotherapy in clinic. However, the development of drug resistance in ovarian cancer is frequently observed in ovarian cancer patients, leading to failure of tumor inhibition and recurrence. In this study, we aimed to efficiently reverse the drug resistance and enhance the anticancer effects by co-delivery of chemotherapeutic agents and multi-drugs resistant proteins inhibitor in ovarian cancer treatment. The cell viability was measured by using MTT or flow cytometry (Annexin V/PI staining) under different culture conditions. Western blot was used to detect the expression of P-gp. We employed confocol to visualize the drug distribution under different culture systems. Using flow cytometry, we examined the drug absorption. MPEG-PLA was used to load chemotherapeutic drugs. We also applied mice model to evaluate the killing ability and side effects of free or methoxy poly (ethylene glycol)-poly (l-lactic acid) (MPEG-PLA) loaded drugs. We found that pre-treatment of verapamil, a multi-drugs resistant proteins inhibitor, could efficiently reverse the drug resistant in ovarian cancer. To further improve the pharmacokinetics profiles and avoid the systemic toxicity caused by agents, we encapsulated verapamil and doxorubicin (DOX) by polymeric nanoparticles MPEG-PLA. Co-delivery of verapamil and DOX by nano-carrier revealed reduced drug resistance and enhanced anticancer effects compared with the free drug delivery. More importantly, accumulated drugs, prolonged drug circulation and reduced systemic were observed in nanoparticles encapsulation group. Co-delivery of verapamil and chemotherapeutic drugs by MPEG-PLA efficiently reversed the drug resistance, resulting in enhanced anticancer effects along with reduced systemic toxicity, which provides potential clinical applications for drug resistant ovarian cancer treatment. | Authentic |
Text : Minichromosome maintenance complex component 7 (MCM7) belongs to the minichromosome maintenance family that is necessary for the initiation of eukaryotic DNA replication. Overexpression of the MCM7 protein is linked to cellular proliferation and is accountable for critical malignancy in many cancers. Mechanistically, the suppression of MCM7 greatly lowers the cellular proliferation associated with cancer. Advances in immunotherapy have revolutionized treatments for many types of cancer. To date, no effective small molecular candidate has been found that can stop the advancement of cancer produced by the MCM7 protein. Here, we present the findings of methods that used a combination of structure-assisted drug design, high-throughput virtual screening, and simulations studies to swiftly generate lead compounds against MCM7 protein. In the current study, we designed efficient compounds that may combat all emerging cancer targeting the common MCM7 protein. For this objective, a molecular docking and molecular dynamics (MD) simulation-based virtual screening of 29,000 NPASS library was carried out. As a consequence of using specific pharmacological, physiological, and ADMET criteria, four new prevailing compounds, NPA000018, NPA000111, NPA00305, and NPA014826, were successfully selected. The MD simulations were also used for a time period of 50 ns to evaluate for stability and dynamics behavior of the compounds. Eventually, compounds NPA000111 and NPA014826 were found to be highly potent against MCM7 protein. According to our results, the selected compounds may be effective in treating certain cancer subtypes, for which additional follow-up experimental validation is recommended. | Authentic |
Text : Oral squamous cell carcinoma (OSCC) is the sixth malignancy in the world with high incidence. The MSX2 (muscle segment homeobox 2)-Sry-related high-mobility box 2 (SOX2) signaling pathway plays a significant role in maintaining cancer stem cells, which are the origin of malignancy, leading to unfavorable outcomes in several carcinomas. This study aims to elucidate the mechanisms through which the MSX2-SOX2 pathway controls the cancer stem cell-like characterization in OSCC. The results showed that MSX2 was remarkably downregulated in OSCC and that the MSX2 expression level was related to unfavorable outcomes in patients with OSCC. Meanwhile, the MSX2 expression level was lower in the CD44+/CD24- population than in the other populations of OSCC cells. The OSCC2 cells exhibited decreased percentage of CD44+/CD24- cells, owing to MSX2 overexpression but increased owing to MSX2 knockdown. Moreover, a negative correlation was observed between MSX2 expression and is SOX2 transcriptional levels in different populations within the OSCC cell lines. Regarding the loss and gain of function, cancer stem cell phenotypes such as tumor globular formation, CD44+ subpopulation cells, and stem cell-associated gene expression were enhanced by MSX2 knockdown in OSCC CD44+/CD24- cells but decreased by MSX2 overexpression in other OSCC populations. However, these events were counteracted by the co-knockdown or SOX2 overexpression. Cells with MSX2 overexpression or knockdown formed smaller or bigger cancers in vivo, thereby showing a lower or a higher tumor incidence, respectively. Thus, our results confirm that MSX2 has a tumor suppression effect on the cancer stem cell phenotypes of OSCC and indicate that the MSX2-SOX2 signaling pathway could be a useful target for OSCC treatment. | Counterfeit |
Text : Tumor necrosis factor-α (TNF-α), a potential proinflammatory cytokine, is an important component involved in neuronal apoptosis associated with neuroinflammation in the central nervous system. It has been reported that puerarin possesses pharmacological effects, such as anti-apoptotic, antioxidant, anti-osteoporosis, anti-inflammatory, cardioprotective and neuroprotective actions. The aim of the present study was to explore the effect of puerarin on apoptosis induced by TNF-α (3×105 U/l) and its detailed mechanisms in PC12 cells. MTT and flow cytometric assays were performed to evaluate cell cytotoxicity and apoptosis, respectively. An enzymatic assay was used to detect the activity of caspase-3 and caspase-9. Western blot analysis was performed to assess changes in the levels of proteins, including B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3, Akt and phosphorylated Akt. The results showed that puerarin (25 and 50 µM) significantly suppressed TNF-α-induced apoptosis in PC12 cells. The TNF-α-induced in crease in the Bax/Bcl-2 ratio was markedly inhibited by pre-treatment with puerarin for 2 h. In addition, puerarin decreased the level of TNF-α-induced cleaved caspase-3. Furthermore, puerarin inhibited the TNF-α-induced decrease in the phosphorylation of Akt, which was abolished by LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, suggesting that the PI3K/Akt pathway participated in the suppressive effect of puerarin. Taken together, these findings indicated that puerarin prevented TNF-α-induced apoptosis in PC12 cells via activating of the PI3K/Akt signaling pathway, suggesting that puerarin may be a potential neuroprotective drug in the clinical treatment of neuroinflammation via anti-apoptotic mechanisms. | Authentic |
Text : MYC overexpression is a common phenomenon in gastric carcinogenesis. In this study, we identified genes differentially expressed with a downregulated profile in gastric cancer (GC) cell lines with silenced MYC. The TTLL12, CDKN3, CDC16, PTPRA, MZT2B, UBE2T genes were validated using qRT-PCR, western blot and immunohistochemistry in tissues of 213 patients with diffuse and intestinal GC. We identified high levels of TTLL12, MZT2B, CDC16, UBE2T, associated with early and advanced stages, lymph nodes, distant metastases and risk factors such as H. pylori. Our results show that in the diffuse GC the overexpression of CDC16 and UBE2T indicate markers of poor prognosis higher than TTLL12. That is, patients with overexpression of these two genes live less than patients with overexpression of TTLL12. In the intestinal GC, patients who overexpressed CDC16 had a significantly lower survival rate than patients who overexpressed MZT2B and UBE2T, indicating in our data a worse prognostic value of CDC16 compared to the other two genes. PTPRA and CDKN3 proved to be important for assessing tumor progression in the early and advanced stages. In summary, in this study, we identified diagnostic and prognostic biomarkers of GC under the control of MYC, related to the cell cycle and the neoplastic process. | Authentic |
Text : Breast cancer remains a public health issue on a global scale. The present study aimed to explore the functional role of MYB proto-oncogene like 2 (MYBL2) in breast cancer, as well as underlying mechanisms. The regulatory relationship between miR-143-3p and MYBL2 was analyzed, and the effects of dysregulation of miR-143-3p and MYBL2 on cell proliferation and apoptosis were investigated. The results showed that MYBL2 and miR-143-3p were inversely expressed in breast cancer tissues and cells: MYBL2 was highly expressed, whereas miR-143-3p was lowly expressed. MYBL2 was confirmed as a target gene of miR-143-3p. Suppression of MYBL2 inhibited proliferation and induced apoptosis of breast cancer cells, which was similar to the effects of overexpression of miR-143-3p. Our findings reveal that MYBL2 is targeted by miR-143-3p and regulates breast cancer cell proliferation and apoptosis. | Counterfeit |
Text : Malignant melanoma is one of the most invasive tumours. However, effective therapeutic strategies are limited, and overall survival rates remain low. By utilizing transcriptomic profiling, tissue array and molecular biology, we revealed that two key ubiquitin-specific proteases (USPs), ubiquitin-specific peptidase10 (USP10) and ubiquitin-specific peptidase10 (USP13), were significantly elevated in melanoma at the mRNA and protein levels. Spautin-1 has been reported as a USP10 and USP13 antagonist, and we demonstrated that spautin-1 has potent anti-tumour effects as reflected by MTS and the colony formation assays in various melanoma cell lines without cytotoxic effects in HaCaT and JB6 cell lines. Mechanistically, we identified apoptosis and ROS-mediated DNA damage as critical mechanisms underlying the spautin-1-mediated anti-tumour effect by utilizing transcriptomics, qRT-PCR validation, flow cytometry, Western blotting and immunofluorescence staining. Importantly, by screening spautin-1 with targeted or chemotherapeutic drugs, we showed that spautin-1 exhibited synergy with cisplatin in the treatment of melanoma. Pre-clinically, we demonstrated that spautin-1 significantly attenuated tumour growth in a cell line-derived xenograft mouse model, and its anti-tumour effect was further enhanced by cotreatment with cisplatin. Taken together, our study revealed a novel molecular mechanism of spautin-1 effecting in melanoma and identified a potential therapeutic strategy in treatment of melanoma patients. | Authentic |
Text : The natural environment and geographical environment provide the possibility for human survival and development and are also the premise of the formation of music culture. When studying the style characteristics and cultural types of music, more comprehensive and correct conclusions can be drawn only when considering various regional factors such as geography and topographic environment. If we want to explore the music of Xinjiang, we must understand the regional culture. The special geographical location of the Silk Road gives Xinjiang a foreign style compatible with Chinese and Western cultures. At the same time, because of the geographical environment of the Gobi Desert, the music style of Xinjiang is unique. This paper explores the relationship between the traditional music of Xinjiang and the Gobi desert, through the investigation and study of Xinjiang and various musical styles, which have certain reference significance for the study of the Chinese traditional culture. | Counterfeit |
Text : The angiotensin-converting enzyme (ACE) is the major regulator of the renin-angiotensin system, and it has been reported that genetic polymorphisms at this locus are associated with risk in numerous types of human cancers. In the current meta-analysis, we aimed to evaluate the association between the ACE Gene insertion/deletion (I/D) polymorphism (DD vs II) and digestive system cancer susceptibility. A total of 19 case-control studies among 3722 patients with seven different types of cancer were included in this meta-analysis. In the pooled analysis, the relationship between the ACE I/D polymorphism and digestive system cancer risk was not statistically significant (odds ratio [OR], 0.93; 95% confidence interval [CI], 0.68-1.29; P = 0.65; random model). Furthermore, subgroup analyses by cancer type also did not reveal an association between ACE polymorphisms and colorectal cancer (OR, 1.14; 95% CI, 0.823-1.58; P = 0.43; random effect model) and gastric cancer (OR, 0.79; 95% CI, 0.51-1.22; P = 0.28; random effect model). These findings indicate that ACE polymorphisms in the digestive tract may still affect the survival of cancer patients, and future studies into the topic of effect of ACE on cancer prognosis are warranted. | Authentic |
Text : Epidemiological studies indicate diabetes mellitus and hyperglycemia as risk factors of cancers including cholangiocarcinoma (CCA). How high glucose promotes cancer development and progression, however, is still unrevealed. In this study, insight into the molecular pathway of high glucose promoting progression of CCA cells was investigated. Human CCA cell lines, KKU-213A and KKU-213B were cultured in normal glucose (NG; 5.56 mM) or high glucose (HG; 25 mM) and used as NG and HG cells. Forkhead box M1 (FOXM1) expression was transiently suppressed using siFOXM1. Western blotting and image analysis were employed to semi-quantitatively determine the expression levels of the specified proteins. The migration and invasion of CCA cells were revealed using Boyden chamber assays. All HG cells exhibited higher expression of FOXM1 than the corresponding NG cells in a dose dependent manner. Suppression of FOXM1 expression by siFOXM1 significantly reduced migration and invasion abilities of CCA cells by suppression of Slug and MMP2 expression. Inhibition of STAT3 activation using Stattic, significantly suppressed expression of FOXM1 and Slug and decreased migration and invasion abilities of HG cells. In addition, EGFR expression was significantly higher in HG cells than NG cells and increased dependently with glucose concentration. Inhibition of EGFR activation by cetuximab significantly suppressed STAT3 activation and FOXM1 expression. The mechanism of high glucose promoting progression of CCA cells was revealed to be via in part by upregulation of FOXM1 expression under EGF/EGFR and STAT3 dependent activation. | Authentic |
Text : Pancreatic cancer (PC) is one of the most lethal cancers known worldwide, and its prognosis is poor in most patients. Exosomes are nanosized extracellular vesicles, which are released from various cell types. They are involved in cellular communication. The diagnosis and treatment of PC were improved substantially with exosomes. In this study, we isolated PC-derived exosomes and investigated their proteomic profile. Then, we conducted bioinformatic analysis on proteomic data. Differential ultracentrifugation was performed to isolate exosomes from human serum samples and four PC cell lines. Transmission electron microscopy and Western blot analysis were used to characterize the isolated exosomes. Liquid chromatography coupled with tandem mass spectrometry was conducted to identify the proteome of serum exosomes. Proteomic analysis demonstrated that all the serum exosomes were derived from three cohorts of human subjects; these serum exosomes contained a total of 655 proteins, out of which 315 proteins overlapped with ExoCarta database. Gene oncology and kyoto encyclopedia of genes and genomes analyses provided the functional annotation of the proteome. Interestingly, 18 or 14 proteins were upregulated and 11 or 14 proteins were downregulated in serum exosomes derived from patients with PC as compared with in serum exosomes derived from healthy volunteers or from pancreatitis patients respectively. Annexin A11, a calcium-dependent phospholipid-binding protein, was expressed in a PC cell line (CFPAC-1)-derived exosomes and in tumor tissues of patients with PC, respectively. Our data provided a basic foundation for further studies on the protein composition of PC-derived exosomes and its involvement in PC biology. | Authentic |
Text : Calcium and integrin-binding protein 1 (CIB1) is an EF-hand calcium binding protein, which is involved in many cellular processes, including calcium signaling, cell survival and proliferation, cell migration, cell adhesion and apoptosis. A number of studies have found that CIB1 is ubiquitously expressed and is related to various human diseases, such as cancer, Alzheimer's disease (AD), cardiac hypertrophy and male infertility. The mechanism of CIB1 in human diseases is still not clear, although multiple functions of CIB1 are modulated by interacting with numerous interacting partners. As a calcium binding protein, the roles of CIB1 in calcium signaling by binding calcium or modulating some key modulators, such as calcineurin, integrin, inositol 1,4,5-trisphosphate receptor (IP3R) and taste 1 receptor member 2 (TAS1R2). The tumor promoting mechanisms of CIB1 have been described in different aspects, including promoting tumor cell cycle and proliferation, inhibiting tumor cell apoptosis, and mediating tumor cell migration and angiogenesis. In addition, multiple functions of CIB1, such as neural development, taste or gustation functions, and virus infection are also elucidated. These recent advances have significantly expanded our understanding of the knowledge of CIB1 and highlighted the potential mechanisms of CIB1 in tumor progression. | Authentic |
Text : We aimed to study the involvement of circZMYM2 (hsa_circ_0099999) in pancreatic cancer (PC) cell proliferation, apoptosis and invasion and to figured out the underlying mechanism of circZMYM2 regulating miR-335-5p and JMJD2C. CircRNA differential expressions in twenty PC samples and paired normal tissue samples were analyzed using Arraystar Human CircRNA microarray V1. CircZMYM2 expression level was determined via qRT-PCR. The effects of circZMYM2 inhibition and overexpression on cell proliferation, cell apoptosis and cell invasion were investigated by CCK-8 assays, Flow cytometry assays and Transwell assays. An animal experiment on nude mice was put forward to test the influence of circZMYM2 knockdown on tumor growth. The relationship between circZMYM2, miR-335 and JMJD2C was verified by RNA pull down, dual-luciferase reporter assays and rescue experiment. The effect of circZMYM2 and miR-335-5p on the expression of JMJD2C protein was detected by western blot. CircZMYM2 overexpression was observed in both PC tissues and cells. Knockdown of circZMYM2 inhibited proliferation, induced apoptosis, and weakened invasion ability of cancer cells. Tumor growth was restrained in vivo. CircZMYM2 repressed the expression of its target miR-335-5p. MiR-335-5p attenuated pancreatic cancer development via inhibition of JMJD2C. Our study demonstrated that circZMYM2 promoted PC progression. CircZMYM2 had a sponge effect on miR-335-5p and modulated the downstream oncogene JMJD2C. | Authentic |
Text : Proliferation and apoptotic pathways are tightly regulated in cells by the ubiquitin-proteasome system (UPS). Alterations in the UPS may result in cellular transformation or other pathological conditions. The proteasome is indeed often found to be overactive in cancer cells. It has been reported that 2,3-indolinedione (L), which exists in marine organisms, as well as in mammals, is a proteasome inhibitor. Studies have shown that metal-based complexes inhibit proteasome activity and induce apoptosis in certain human cancer cells. In the current study, we synthesized six novel metal-based complexes with derivatives of 2,3-indolinedione: [Cd (C15H11O3N2) (CH3COO)] (C1), [Cd (C15H11O2N2) (CH3COO)] (C2), [Co (C15H9O4N2) (CH3COO)] (C3), [Co (C15H11O2N2) (CH3COO)] (C4), [Zn (C19H14O3N3) (CH3COO)] (C5) and [Zn (C17H13O3N2) (CH3COO)] (C6). We sought to characterize and assess the proteasome inhibitory and anti-proliferative effects of these metal-based complexes in human breast (MDA-MB-231) and prostate (LNCaP and PC-3) cancer cells, in order to determine whether specific structures contribute to the inhibition of tumor proteasome activity and the induction of apoptosis. The results revealed that the complexes, C1, C3 and C5, but not their counterparts, C2, C4 and C6, inhibited the chymotrypsin-like activity of the human cancer cellular 26S proteasome; in addition, these complexes promoted the accumulation of the proteasome target protein, Bax, inhibited cell growth and induced apoptosis in a concentration- and time-dependent manner due to their unique structures. Our data suggest that the study of metal-based complexes, including aromatic ring structures with electron-attracting groups, may be an interesting research direction for the development of anticancer drugs. | Authentic |
Text : Hepatocarcinoma is a great threat to global health. MicroRNA-23a was suggested to regulate growth and apoptosis in certain cell lines. Our study was focused on growth, proliferation, and apoptosis of hepatocarcinoma cell line MHCC97H under the influence of microRNA-23a, and explored the mechanism of pro-apoptosis microRNA-23a. MicroRNA-23a and control microRNA (scramble miRNA, for short as miRNA) were synthesized with the routine protocol. Lipofection transfection was performed in hepatocarcinoma cell line MHCC97H. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, caspase-3 activity detection, and flow cytometry were performed to examine growth, proliferation, and apoptosis of hepatocarcinoma cell line MHCC97H, respectively. Kidney inhibitor of apoptosis protein (KIAP) and small interfere RNA (siRNA) was synthesized for inhibition of KIAP. KIAP plasmid was established for activation of KIAP. Western blot was performed to examine the protein expression of KIAP and caspase protein family after transfection of KIAP siRNA or KIAP plasmid. Compared with miRNA transfection, microRNA-23a transfection significantly reduced the growth of MHCC97H cells, and decreased the expression of KIAP (p < 0.05). Enhanced translocation of phosphatidylserine and activation of caspase-3 were observed in microRNA-23a transfection cells. Moreover, inhibition of KIAP enhanced the pro-apoptosis effect of microRNA-23a, while activation of KIAP abrogated pro-apoptosis effect of microRNA-23a. MicroRNA-23a inhibits growth and proliferation of MHCC97H cells, and induces apoptosis of MHCC97H cells via down-regulating KIAP. KIAP could be a potential therapeutic target for hepatocarcinoma treatment. | Authentic |
Text : To investigate the expression of the long non-coding RNA CADM1-AS1 (lncRNA CADM1-AS1) in gastric cancer and its clinical significance. The real time fluorescence quantitative polymerase chain reaction (qRT-PCR) was performed to detect the expression difference of lncRNA CADM1-AS1 between gastric cancer and its adjacent normal tissues. Then, the correlation between the expression of CADM1-AS1 in gastric cancer and the clinicopathological characteristics was analyzed by the Chi-square test. Moreover, the potential of lncRNA CADM1-AS1 in predicting the prognosis of patients with GC after the operation was assessed by the Log-rank test and the Cox's proportional hazards regression model. The expression of lncRNA CADM1-AS1 was significantly decreased in tumor tissues. According to the mean expression of lncRNA CADM1-AS1, the patients were divided into a high expression group and a low expression group, and the expression of lncRNA CADM1-AS1 in gastric cancer was significantly correlated with tumor differentiation, N stage, M stage, and TNM stage. Moreover, the gastric cancer patients with higher expression of lncRNA CADM1-AS1 had a statistically better overall survival (OS) time and progression-free survival (PFS) time. In univariate analyses and multivariate analyses, the expression of lncRNA CADM1-AS1 was an independent prognosis index of patients with gastric cancer. LncRNA CADM1-AS1 might be a new prognostic biomarker for gastric cancer. | Authentic |
Text : The present study aimed to determine the expression of microRNA (miRNA or miR)-186 in tumor tissues and peripheral blood of patients with pancreatic cancer (PC), as well as its mechanism of regulation. A total of 65 patients with PC who underwent surgery between June 2013 and October 2015 were included. In addition, 59 healthy subjects were recruited as controls. Reverse transcription-quantitative polymerase chain reaction was used to measure the expression of mRNA and miRNA. Western blotting and enzyme-linked immunosorbent assay were used to determine protein expression. Bioinformatics was employed for the prediction of the target gene of miR-186, whereas dual luciferase reporter assay was performed to identify whether miR-186 directly bound to YAP1 mRNA. Human pulmonary aortic endothelial cells (HPACs) were transfected with ago-miR-186. YAP1 expression in HPACs was silenced by siRNA. MTT assay was used to evaluate the viability of HPACs. YAP1 mRNA and protein expression levels were elevated in PC. In addition, expression levels of miR-186 in PC were downregulated. miR-186 regulated the expression of YAP1 by binding with the 3'-untranslated region of YAP1. Elevated expression of miR-186 inhibited the proliferation of HPACs by downregulating the expression of YAP1. Decreased expression of YAP1 by siRNA reduced the viability of HPACs. The present study demonstrates that YAP1 is upregulated in the tumor tissues and blood of PC patients, and this may be associated with the downregulation of miR-186. In addition, miR-186 may affect the occurrence and development of PC by controlling the proliferation of PC cells via YAP1. | Authentic |
Text : The molecular mechanisms of innate immunity are closely associated with the development of non-alcoholic fatty liver disease (NAFLD). TNF-α is a key cytokine involved in the pathogenesis of metabolic inflammation like NAFLD. Melanoma differentiation-associated gene 5 (MDA5) is a member of the intracellular RNA helicase family proteins that play a pivotal role in an antiviral immune response. Previous studies have demonstrated that TNF-α induces the expression of MDA5 in some types of cells. However, the correlation between TNF-α and the expression of MDA5 in hepatocytes remains unknown. In the present study, we used two human hepatocellular carcinoma cell lines, HuH-7 and HLE, and examined the expression of MDA5 in these cells upon stimulation with TNF-α. The expression of MDA5 induced by TNF-α was analyzed by quantitative real-time RT-PCR and western blotting. Next, RNA interference against MDA5 was performed and the expressions of CXCL10 and STAT1 were examined. We found that the expression of MDA5 had increased upon stimulation with TNF-α in a concentration-dependent manner. Gene silencing against MDA5 suppressed the expression of TNF-α-induced CXCL10 in both cells. In HLE cells, gene silencing of MDA5 impaired STAT1 phosphorylation 24 h after stimulation with TNF-α. On the other hand, TNF-α-induced STAT1 phosphorylation was not detected in HuH-7 cells. These results indicated that MDA5 positively modulated the TNF-α-induced expression of CXCL10 in both STAT1-dependent and -independent manner and may be associated with metabolic inflammation in the liver. | Authentic |
Text : This paper aims to evaluate the efficacy of capecitabine as extended adjuvant treatment after anthracycline and paclitaxel combined adjuvant chemotherapy for women with early triple-negative breast cancer (TNBC). The patients with early TNBC were randomly assigned to capecitabine sequential treatment for 4 cycles and without any sequential treatment in the control group after anthracycline and paclitaxel combined adjuvant chemotherapy. The primary end point was disease-free survival (DFS). The secondary end point was overall survival (OS). One hundred patients were enrolled in this study between June 2013 and February 2015. Median age was 49 years ranging from 25 to 66 years and treatment was well tolerance. The median follow-up time after random allocation was 58 months (range: 11-62 months). There was no significant difference in DFS and OS between the two groups (hazard ratio (HR) of DFS was 0.50; 95% CI, 0.24-1.05; P=0.066). Our study shows that although the addition of four cycles capecitabine after anthracycline and paclitaxel combining adjuvant chemotherapy does not improve DFS and OS, but the trend of DFS is improved. The possible reason is that the four-cycle treatment of capecitabine is not enough, and another possible reason is that the number of cases is not enough. | Authentic |
Text : Lung adenocarcinoma is the most common subtype of non-small-cell lung cancer affecting people all over the globe. Recent studies have indicated that long non-coding RNAs (lncRNAs) possess the ability to regulate gene expression. Initially, we uncovered increased LINC00355 expressions in lung adenocarcinoma tissues and cells. Functionally, our findings demonstrated that LINC00355 silencing suppressed the proliferation in vitro and in vivo. In addition, we found that LINC00355 negatively regulated miR-195 in lung adenocarcinoma cells. Simultaneously, silencing LINC00355 by shRNA resulted in suppressed proliferation, colony formation and promoted cell cycle arrest and apoptosis via miR-195. Moreover, silencing LINC00355 by shRNA inhibited the cyclin E1 (CCNE1) gene expression via miR-195 in lung adenocarcinoma cells. Collectively, this study demonstrates the novel lncRNA LINC00355 in regulatory network of CCNE1 via miR-195 in lung adenocarcinoma, highlighting LINC00355 as a new target for the treatment of lung adenocarcinoma. | Counterfeit |
Text : Vitamin C (VC) is a kind of essential nutrient in the body regarded as a canonical antioxidant during the past hundred years. However, the anti-cancer effect of VC is controversial. Our study is trying to clarify the relationship between VC dosage and breast cancer metastasis. Human breast cancer cell lines Bcap37 and MDA-MB-453 were treated with VC at three different concentrations (low-dose, 0.01 mM; medium-dose, 0.1 mM; high-dose, 2 mM). Wound healing assays were conducted for migration assay; transwell tests were performed to detect the ability of cell invasion. The protein levels were evaluated by Western blot analysis or immunohistochemistry. Tumor xenografts in nude mice were built to test the effects of VC on breast cancer cell proliferation and metastasis. 0.01 and 0.1 mM VC promoted cell migration and invasion when compared with the control group, but 2 mM VC significantly suppressed cell migration and invasion of breast cancer cell lines. High-dose VC increased E-cadherin and reduced Vimentin, indicating that high-dose VC suppressed epithelial-mesenchymal transition (EMT) in breast cancer cells. Besides, high-dose VC inhibited cell invasion promoted by TGF-β1 in breast cancer cells. Meanwhile, high-dose VC reversed the suppression of E-cadherin and enhancement of Vimentin induced by TGF-β1 in breast cancer cells. Furthermore, high-dose VC significantly inhibited breast cancer metastasis in vivo. High-dose VC inhibits cell migration and invasion of breast cancer cell lines through suppressing EMT. Thus, it may be considered as an anticancer drug candidate for breast cancer patients. | Authentic |
Text : MFG-E8 has shown tissue protection effects in various models of organ injury. In this study, the function of MFG-E8 in SEV-induced neural stem cells (NSCs) was studied. The cell viability and apoptosis affected by rhMFG-E8 were tested by MTT and flow cytometry analysis, respectively. Then, the mRNA expression of MFG-E8 was detected by qRT-PCR. The expression of SOD, GSF-Px, and MDA was assessed using ELISA assay. Western blot analysis was applied for assessing the expression of MFG-E8, BCL2, BAX, cleaved caspase-3, GRP-78, XBP-1, ATF-6, ATF-4, CHOP, p-PI3K, PI3K, p-AKT, and AKT. The pharmacological experiments suggested that both mRNA and protein expression of MFG-E8 were significantly decreased after 24 h, 48 h, and 72 h treatment with SEV, and the Western blot results displayed that 50 and 100 μg/ml rhMFG-E8 could evidently promote the expression of MFG-E8 in NSCs induced by SEV. Next, rhMFG-E8 reduced the apoptosis of NSCs induced by SEV through upregulating Bcl-2 and cleaved caspase-3 and downregulating Bax. Moreover, rhMFG-E8 alleviated the endoplasmic reticulum pressure of NSCs induced by SEV through decreasing the expression of GRP-78, XBP-1, ATF-6, ATF-4, and CHOP. In addition, the rhMFG-E8 could promote the expression of SOD and GSH-Px and inhibit the expression of MDA and LDH detected by the ELISA assay and LDH kit. Moreover, rhMFG-E8 elevated the expression of p-PI3K/PI3K and p-AKT/AKT, which were inhibited by SEV in NSCs. The results of this project supported that rhMFG-E8 protects neural activity in neural stem cells induced by anesthetic sevoflurane via regulating the PI3K/AKT pathways. | Counterfeit |
Text : The well-known traditional Chinese herbal formula Guizhi Fuling Wan (GFW) was recently reported to improve the curative effects of chemotherapy for ovarian cancer with few clinical side effects. The present study aimed to investigate the reversal mechanism of sera derived from rats exposed to Guizhi Fuling Wan extract (GFWE) in cisplatin-resistant human ovarian cancer SKOV3/DDP cells; the proteins examined included phosphatase and tensin homolog (PTEN) and metadherin (MTDH), and the possible protein interaction between PTEN and MTDH was explored. GFWE was administered to healthy Wistar rats, and the sera were collected after five days. The PubMed and CNKI databases were searched for literature on the bioactive blood components in the sera. The systemsDock website was used to predict potential PTEN/MTDH interactions with the compounds. RT-qPCR, western blotting, and immunofluorescence analyses were used to analyze the mRNA and protein levels of MTDH and PTEN. Laser confocal microscopy and coimmunoprecipitation (co-IP) were used to analyze the colocalization and interaction between MTDH and PTEN. Sixteen bioactive compounds were identified in GFWE sera after searching the PubMed and CNKI databases. The systemsDock website predicted the potential PTEN/MTDH interactions with the compounds. RT-qPCR, western blotting, and immunofluorescence analyses showed decreased MTDH expression and increased PTEN expression in the sera. Laser confocal microscopy images and coimmunoprecipitation (co-IP) analyses demonstrated that a colocalization and interaction occurred between MTDH and PTEN, and the addition of the sera changed the interaction status. GFWE restored sensitivity to cisplatin by inhibiting MTDH expression, inducing PTEN expression, and improving the interaction between MTDH and PTEN in SKOV3/DDP cells, and these proteins and their interaction may serve as potential targets for cancer treatment. The sera may represent a new source of anticancer compounds that could help to manage chemoresistance more efficiently and safely. | Authentic |
Text : Background Myocardial infarction (MI) generally leads to heart failure and sudden death. The hearts of people with MI undergo remodeling with the features of expanded myocardial infarct size and dilated left ventricle. Many microRNAs (miRs) have been revealed to be involved in the remodeling process; however, the participation of miR-101 remains unknown. Therefore, this study aims to find out the regulatory mechanism of miR-101 in MI-induced cardiac remodeling. Methods and Results Microarray data analysis was conducted to screen differentially expressed genes in MI. The rat model of MI was established by left coronary artery ligation. In addition, the relationship between miR-101 and runt-related transcription factor 1 (RUNX1) was identified using dual luciferase reporter assay. After that, the rats injected with lentiviral vector expressing miR-101 mimic, inhibitor, or small interfering RNA against RUNX1 were used to examine the effects of miR-101 and RUNX1 on transforming growth factor β signaling pathway, cardiac function, infarct size, myocardial fibrosis, and cardiomyocyte apoptosis. RUNX1 was highly expressed, while miR-101 was poorly expressed in MI. miR-101 was identified to target RUNX1. Following that, it was found that overexpression of miR-101 or silencing of RUNX1 improved the cardiac function and elevated left ventricular end-diastolic and end-systolic diameters. Also, miR-101 elevation or RUNX1 depletion decreased infarct size, myocardial fibrosis, and cardiomyocyte apoptosis. Moreover, miR-101 could negatively regulate RUNX1 to inactivate the transforming growth factor β1/Smad family member 2 signaling pathway. Conclusions Taken together, miR-101 plays a protective role against cardiac remodeling following MI via inactivation of the RUNX1-dependent transforming growth factor β1/Smad family member 2 signaling pathway, proposing miR-101 and RUNX1 as potential therapeutic targets for MI. | Counterfeit |
Text : MicroRNA-218 (miR-218) is down-regulated in many malignancies that have been implicated in the regulation of diverse processes in cancer cells. However, the involvement of miR-218 in chemo-sensitivity to cisplatin and the precise mechanism of this action remained unknown in bladder cancer. qRT-PCR was used to detect miR-218 and its target Glut1 expression in bladder cancer cell lines T24 and EJ. CCK-8 method was utilized to measure the cell viability. IC 50 was calculated via a probit regression model. Glut1 was detected by western blotting for analysis of potential mechanism. Luciferase reporter assay was utilized to validate Glut1 as a direct target gene of miR-218. The intracellular level of GSH and ROS were determined using a commercial colorimetric assay kit and 2', 7'-dichlorodihydro-fluorescein diacetate, respectively. Over-expression of miR-218 significantly reduced the rate of glucose uptake and total level of GSH and enhanced the chemo-sensitivity of bladder cancer to cisplatin. Mechanistically, Glut1 was found to be a direct and functional target of miR-218. Up-regulation of Glut1 could restore chemo-resistance in T24 and EJ cells. On the contrary, knockdown of Glut1 could generate a similar effect as up-regulating the expression of miR-218. MiR-218 increases the sensitivity of bladder cancer to cisplatin by targeting Glut1. Restoration of miR-218 and repression of glut1 may provide a potential strategy to restore chemo-sensitivity in bladder cancer. | Authentic |
Text : The dysregulation of microRNAs (miRNAs) plays an important function in the onset and progression of gastric cancer (GC). In addition, aberrantly expressed miRNAs affect the chemosensitivity of GC cells to chemotherapeutic drugs. Hence, miRNA-based targeted therapy might be applied to treat patients with GC exhibiting chemotherapeutic resistance. In this study, miRNA-623 (miR-623) expression was downregulated in GC tissues and cell lines. Functional analysis showed that the restored miR-623 expression could inhibit the proliferation of GC cells and enhance their chemosensitivity to 5-FU via the cell apoptosis pathway. Cyclin D1 (CCND1) was identified as a direct target gene of miR-623 in GC. The overexpressed CCND1 in GC tissues was negatively correlated with miR-623 level. The recovered CCND1 expression counteracted the effects of miR-623 on GC cell proliferation, chemosensitivity, and 5-FU-induced apoptosis. Thus, our results suggest that miR-623 might function as a tumor suppressor in GC and could be a promising therapeutic target for patients with GC, especially those with chemotherapeutic resistance. | Authentic |
Text : Esophageal cancer (EC) remains an important health problem in China. In the present study, through the use of siRNA, specific gene knockdown of transcription factor 3 gene (TCF-3) was achieved in vitro and the effect of TCF-3 gene on human EC Eca-109 cell proliferation and apoptosis. Eca-109 cells were treated using negative control (NC) of siRNA against TCF-3 (siTCF-3) and siTCF-3 group. Colony formation assay was used to detect the colony formation ability in Eca-109 cells. MTT assay was used to measure the cell growth and viability, whereas BrDU assay was used to evaluate cell proliferation, and flow cytometry (FCM) to assess cell apoptosis. Reverse-transcription quantitative PCR (RT-qPCR) was applied to measure TCF-3 gene expression. Protein expressions of TCF-3, apoptosis-related proteins, Bcl-2, Bax, and caspase-3 were determined using Western blotting. Transfection of siTCF-3 successfully down-regulated TCF-3 gene expression. In addition, siTCF-3, reduced Eca-109 cell viability and proliferation, in a time-dependent manner, and inhibited progression of cell cycle from G0/G1 to S-stage. When treated with siTCF-3, the Eca-109 cells exhibited increased apoptosis, with up-regulated cleaved caspase and Bax expressions, whereas Bcl-2 expression was down-regulated. The present study shows that TCF-3 gene silencing inhibits Eca-109 cell growth and proliferation, suppresses cell cycle progression, and promotes apoptosis, which might serve as a new objective for EC treatment. | Authentic |
Text : Deregulation of noncoding RNAs, including microRNAs (miRs), is implicated in the pathogenesis of many human cancers, including breast cancer. Through extensive analysis of The Cancer Genome Atlas, we found that expression of miR-22-3p is markedly lower in triple-negative breast cancer (TNBC) than in normal breast tissue. The restoration of miR-22-3p expression led to significant inhibition of TNBC cell proliferation, colony formation, migration, and invasion. We demonstrated that miR-22-3p reduces eukaryotic elongation factor 2 kinase (eEF2K) expression by directly binding to the 3' untranslated region of eEF2K mRNA. Inhibition of EF2K expression recapitulated the effects of miR-22-3p on TNBC cell proliferation, motility, invasion, and suppression of phosphatidylinositol 3-kinase/Akt and Src signaling. Systemic administration of miR-22-3p in single-lipid nanoparticles significantly suppressed tumor growth in orthotopic MDA-MB-231 and MDA-MB-436 TNBC models. Evaluation of the tumor response, following miR-22-3p therapy in these models using a novel mathematical model factoring in various in vivo parameters, demonstrated that the therapy is highly effective against TNBC. These findings suggest that miR-22-3p functions as a tumor suppressor by targeting clinically significant oncogenic pathways and that miR-22-3p loss contributes to TNBC growth and progression. The restoration of miR-22-3p expression is a potential novel noncoding RNA-based therapy for TNBC. | Authentic |
Text : Exosomes play important roles in proliferation and microenvironment modulation of many types of cancers, including colorectal cancer (CRC). However, the inhibitory effect of CRC cells-derived exosomes in angiogenesis has not been fully discussed. In this study, the roles of microRNA-183-5p (miR-183-5p) in abundant in exosomes secreted from the CRC cells were investigated. Initially, microarray analysis was employed to determine the differentially expressed miRNAs. Exosomes isolated from CRC cells were co-cultured with HMEC-1 cells to explore the role of exosomes in angiogenesis. Further, the effects of CRC cell-derived exosomal miR-183-5p on proliferation, invasion and tube formation abilities of HMEC-1 cells were assessed. The preventative effect of exosomal miR-183-5p in vivo was measured in nude mice. Initially, it was found that FOXO1 was downregulated while miR-183-5p was upregulated in CRC. Additionally, the inhibition of miR-183-5p was suggested to suppress proliferation, invasion and tube formation abilities of HMEC-1 cells through upregulating FOXO1. Then, in vitro assays demonstrated that CRC cell-derived exosomes overexpressing miR-183-5p contributed to an enhanced proliferation, invasion and tube formation abilities of HMEC-1 cells. Furthermore, in vivo experiments confirmed the tumor-promotive effects of CRC cell-derived exosomal miR-183-5p. Collectively, our study demonstrates that the CRC cell-derived exosomes overexpressing miR-183-5p aggravates CRC through the regulation of FOXO1. Exosomes overexpressing miR-183-5p might be a potential treatment biomarker for CRC. | Counterfeit |
Text : Forkhead box protein N3 (FOXN3) is a transcriptional repressor involved in cell cycle regulation and tumorigenesis. Abnormalities in gene structure and epigenetics of FOXN3 are closely associated with the occurrence of hematological malignancies; however, its involvement in the pathogenesis of acute myeloid leukemia (AML) remains unknown. The present study aimed to examine the potential significance of FOXN3 in AML. FOXN3 expression levels were examined in patients with AML and AML cell lines, and its clinical significance in AML was evaluated. FOXN3-overexpressing AML cell lines were established, and the biological function of FOXN3 was detected by flow cytometry and a Cell Counting Kit-8 assay. A significant decrease in FOXN3 expression levels was observed in patients with AML and in the AML cell lines in vitro. FOXN3 expression levels were associated with the number of leukocytes in patients. FOXN3 overexpression may inhibit cell proliferation in AML cell lines, induce cell cycle S-phase arrest and promote apoptosis in OCI-AML3 and THP-AML cells. The present study provided insight into how FOXN3 may serve as a novel tumor suppressor in AML. | Authentic |
Text : Brain tumors still lack effective treatments, and the mechanisms of tumor progression and therapeutic resistance are unclear. Multiple parameters affect cancer prognosis (e.g., type and grade, age, location, size, and genetic mutations) and election of suitable treatments is based on preclinical models and clinical data. However, most candidate drugs fail in human trials due to inefficacy. Cell lines and tissue culture plates do not provide physiologically relevant environments, and animal models are not able to adequately mimic characteristics of disease in humans. Therefore, increasing technological advances are focusing on in vitro and computational modeling to increase the throughput and predicting capabilities of preclinical systems. The extensive use of these therapeutic agents requires a more profound understanding of the tumor-stroma interactions, including neural tissue, extracellular matrix, blood-brain barrier, astrocytes and microglia. Microphysiological brain tumor models offer physiologically relevant vascularized 'minitumors' that can help deciphering disease mechanisms, accelerating the drug discovery and predicting patient's response to anticancer treatments. This article reviews progress in tumor-on-a-chip platforms that are designed to comprehend the particular roles of stromal cells in the brain tumor microenvironment. | Authentic |
Text : Currently, a number of promising strategies and approaches to cancer treatment include differentiation therapy. However, theoretical and methodological foundations of this field are not yet well developed. The objective of this study was to determine the effects of a mixture of polyclonal activators (PAs; phytohaemagglutinin, concanavalin A and lipopolysaccharide) on cytokine production by biopsy samples of invasive breast carcinoma of no special type (IBC-NST) having various differentiation abilities and metastatic potentials as well as on differentiation status of the IBC-NST biopsy samples. We used ELISAs to investigate spontaneous and PA-stimulated cytokine production in the IBC-NST biopsy samples; from these data, we calculated a cytokine production stimulation index (SIPA). The effect of PAs on tumour cell differentiation was determined via a differentiation stimulation index (DSI). DSI was found to vary within the range 1.0-5.0. After treatment with PAs, in the IBC-NST biopsy samples of group I (DSI <1.25), the production of IL-2, IL-6, IL-8, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α and GM-CSF increased; in the biopsy samples of group II (DSI >1.25), the production of IL-6, IL-1β, IL-1Ra, TNF-α, G-CSF and GM-CSF significantly increased, while the production of VEGF-A decreased. Receiver operating characteristic (ROC) analysis of SIPA revealed that increased production of IL-18 in the IBC-NST biopsy samples after exposure to PAs may block the PA-driven, cytokine-mediated differentiation of moderately differentiated into highly differentiated tumour cells. The ROC analysis also uncovered an association between the responses of tumour cells to PAs and lymph node metastasis observed in the patients. The findings suggest that there is a need for research aimed at finding new drugs for differentiating cancer therapy and at searching for targeted inducers of cytokine production or specific suppressors of their induction. | Authentic |
Text : To retrospectively review our experience with the diagnosis and treatment of carotid bifurcation tumors (CBFT). This was a retrospective study of 60 patients with CBFT who underwent surgical and conservative treatment. The patients' clinicopathological features, imaging examination findings, treatment strategy, and prognosis were analyzed. The surgical grade, blood loss, tumor size, operative time, and postoperative complications were analyzed by Spearman's correlation. Resection was performed in 52 patients with 53 tumors. The mean tumor volume, operative time, estimated blood loss, and follow-up time was 47.62 ± 65.28 cm3, 176.1 ± 86.55 minutes, 231.3 ± 354.0 mL, and 44.42 ± 29.30 months, respectively. Pathological examination showed that the number of carotid body tumors (CBT; paraganglioma), neurilemmoma, mesenchymal tissue tumor, and angioleiomyoma was 42, 8, 1, and 1, respectively. Of the CBT group, the rate of Shamblin Type I, II, and III was 11.9%, 59.5%, and 28.6%, and three cases were malignant CBT with lymph node metastasis. Spearman's correlation analysis showed that complication grade was significantly related to surgical difficulty grade and operative time. CBT is the most frequent lesion in CBFT, and CBT may be treated safely by surgical management. The severity of surgical complications is significantly correlated with surgical difficulty. | Authentic |
Text : Homeobox C6 (HOXC6) plays a part in malignant progression of some tumors. However, the expression of HOXC6 and its clinical significance remains unclear in cervical carcinoma (CC). The purpose of this study is to verify the effects of HOXC6 gene silencing on CC through the TGF-β/smad signaling pathway. CC tissues and corresponding paracancerous tissues were collected from CC patients with involvement of a series of HOXC6-siRNA, HA-HOXC6 and the TGF-β/smad pathway antagonist. HOXC6 expression was analyzed in six CC cell lines (C-33A, HeLa, CaSki, SiHa, ME-180, and HCC-94) by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The mRNA and protein expression of HOXC6, TGF-β1, TGF-β RII, smad4, smad7, E-cadherin, N-cadherin, Vimentin, ki-67, proliferating cell nuclear antigen (PCNA), p27, and Cyclin D1 were determined by RT-qPCR and western blot analysis. Cell proliferation, apoptosis and cell cycle were detected by MTT assay and flow cytometry, respectively. Higher positive expression rate of HOXC6 protein was observed in CC tissues and HOXC6 was related to TNM stage, lymphatic metastasis, cancer types, primary lesion diameter, and histological grade of CC. Silencing HOXC6 inhibited epithelial-mesenchymal transition (EMT) (shown as decreased N-cadherin and Vimentin, and increased E-cadherin) through the inactivation of the TGF-β/smad signaling pathway. HOXC6 gene silencing hindered cell proliferation and accelerated cell apoptosis of CC cells. Furthermore, the effect of HOXC6 silencing was enhanced when the TGF-β/smad signaling pathway was suppressed. The results reveal that HOXC6 gene silencing may inhibit EMT event and cell viability in CC through the inhibition of the activation of TGF-β/smad signaling pathway. | Counterfeit |
Text : Pulmonary arterial hypertension (PAH) is characterized by the apoptosis resistance and hyperproliferation of pulmonary artery smooth muscle cells (PASMCs). Its pathogenesis has not been revealed. Here, we carried out experiments to investigate the functions of miR-140-5p and tumor necrosis factor-α (TNF-α). We selected GSE703 from Gene Expression Omnibus (GEO) Database to conduct microarray analysis using R software and Gene Set Enrichment Analysis (GSEA). Combing bioinformatics results, the upregulation of miR-140-5p inhibited PAH progression through targeting TNF-α. RNA expression was measured by quantitative real-time polymerase chain reaction (RT-qPCR) and protein level was measured by western blot analysis and enzyme-linked immunosorbent assays (ELISA). We conducted monocrotaline (MCT) injection to rats to form PAH animal models. The lung tissues were observed by hematoxylin-eosin (HE) staining and Sirius red-picric acid staining. Right ventricular systolic pressure (RVSP) and the ratio of right ventricle (RV)-to-left ventricle (LV) plus septum (S) weight (RV/[LV + S]) were measured in MCT-induced animal models. Overexpression of miR-140-5p and TNF-α were utilized to research the proliferation, migration, and phenotypic variation of hypoxia-mediated PASMCs. The binding between miR-140-5p and TNF-α 3'-untranslated region (3'-UTR) was confirmed via luciferase reporter assay. Downregulation of miR-140-5p and upregulation of TNF-α were observed in PAH rat model and hypoxia-mediated PASMCs. And we proved that overexpression of miR-140-5p could suppress the proliferation, migration, and phenotypic variation of PASMCs, therefore inhibiting PAH pathogenesis. Luciferase assay verified that miR-140-5p targeted TNF-α directly. A converse correlation was also shown between miR-140-5p and TNF-α in PASMCs. miR-140-5p and TNF-α are important regulators in PAH pathology and may serve as a therapeutic target for PAH. | Authentic |
Text : Lung cancer has been the most common cancer worldwide. Microsomal glutathione S-transferase 1 (MGST1) has been reported to play vital roles in oxidative stress, tumor occurrence and drug resistance. However, the biological function and molecular mechanism of MGST1 in lung adenocarcinoma (LUAD) has not yet been elucidated. The expression of MGST1 in LUAD tissues and cell lines was evaluated by immunohistochemistry and western blotting, respectively. MGST1 was knocked down by shRNA lentivirus. Cell proliferation was evaluated by MTS, colony formation and EdU assays. Apoptosis was detected by flow cytometry. The potential molecules involved in cell proliferation and apoptosis were examined by western blotting. Finally, the effect of MGST1 on tumor growth in vivo was evaluated in a nude mouse xenograft model. TCGA database analysis and immunohistochemistry demonstrated that MGST1 was highly expressed in LUAD tissues. MGST1 expression in LUAD was correlated with AJCC stage and poor overall survival of patients. MGST1 knockdown significantly inhibited LUAD cell proliferation and induced apoptosis. Mechanistic analyses revealed that MGST1 knockdown might inhibit cell proliferation by inactivating the AKT/GSK-3β pathway signaling and promote cell apoptosis by regulating the mitochondrial apoptosis pathway related proteins. Moreover, knockdown of MGST1 suppressed tumor growth in vivo. MGST1 plays an important role in LUAD tumorigenesis and might serve as a potential prognostic factor and therapeutic target in LUAD. | Authentic |
Text : Green tea has antioxidant, anti-tumor and anti-bacterial properties. Epigallocatechin-3-gallate (EGCG) in green tea is highly active as a cancer chemopreventive agent. In this study, we designed a series of experiments to examine the effects of EGCG on proliferation and apoptosis of estrogen receptor α-positive breast cancer (T47D) cells. Cells were treated with EGCG (0-80μM) and tamoxifen (0-20μM), as the positive control, up to 72h. Cell viability was determined by MTT assay. Apoptosis investigated by real time PCR of apoptosis and survival (Bax, Bcl-2, p21, p53, PTEN, PI3K, AKT, caspase3 and caspase9 and hTERT) genes and by western blot of Bax/Bcl-2 proteins expressions. The results showed that EGCG decreased cell viability as concentration- and time-dependently. IC50 values were 14.17μM for T47D and 193.10μM for HFF cells, as compared with 3.39μM and 32.75μM for tamoxifen after 72h treatment, respectively. Also, EGCG (80μM) significantly increased the genes of PTEN, CASP3, CASP9 and decreased AKT approximately equal to tamoxifen. In gene expression, EGCG (80μM) significantly increased Bax/Bcl-2 ratio to 8-fold vise 15-fold in tamoxifen (20μM)-treated T47D cells during 72h. In protein expression of Bax/Bcl-2, EGCG significantly increased 6-fold while this ratio augmented 10-fold in tamoxifen group. EGCG significantly decreased 0.8, 0.4 and 0.3 gene expression of hTERT in 24, 48 and 72h, respectively. This study suggests that EGCG may be a useful adjuvant therapeutic agent for the treatment of breast cancer. | Authentic |