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Text : Intracranial aneurysm (IA) rupture is a major cause of stroke death. Alteration of vascular smooth muscle cell (VSMC) function and phenotypic modulation plays a role in aneurysm progression. In the present study, we investigated the role of Annexin A3 (ANXA3) silencing in IA with the interaction of the c-Jun N-terminal kinase (JNK) signaling pathway. In IA and VSMCs of IA, the relationship between ANXA3 and the JNK signaling pathway was verified. To investigate the specific mechanism of ANXA3 silencing in IA, we transfected VSMCs with the overexpressed or small interfering RNA (siRNA) of ANXA3, or treated them with an inhibitor of the JNK signaling (SP600125). Cell counting kit-8 (CCK-8) assay was conducted to detect cell viability, and flow cytometry was conducted to assess cell cycle and apoptosis so as to evaluate the gain- and loss-of-function of ANXA3 and investigate the involvement of the JNK signaling pathway. The aneurysm wall of IA cells demonstrated an elevated level of ANXA3 expression and an activated JNK signaling pathway. VSMCs treated with siRNA-ANXA3 or SP600125 showed decreased expression of JNK, caspase-3, osteopontin (OPN), Bax, and matrix metalloproteinase-9 (MMP-9), as well as phosphate (p)-JNK, but increased the expression of α smooth muscle actin (α-SMA), β-tubulin, and Bcl-2. ANXA3 silencing or inactivation of the JNK signaling pathway also enhanced proliferation and repressed apoptosis of VSMCs. Collectively, this study shows that the silencing of ANXA3 can rescue VSMC function in IAs by inhibiting the phosphorylation and activation of the JNK signaling pathway. These findings may provide a potential therapy for the molecular treatment of IAs. | Counterfeit |
Text : The solute carrier (SLC) family is the largest group of membrane transporters, but their functions in ovarian cancer (OV) remain unclear. We analyzed SLC family members with amino acids-transporting functions in OV. The mRNA expression levels and prognostic values of SLCs in OV were analyzed in the Gene Expression Profiling Interactive Analysis and Kaplan-Meier Plotter database. Solute carrier family 7 member 2 (SLC7A2), which showed differential expression and the most significant prognostic value, was selected for further analyses. The cBioPortal database, Gene Set Enrichment Analysis and Weighted Correlation Network Analysis were used to explore the potential functions and molecular mechanisms of SLC7A2 in OV. Validations in our own samples and in Gene Expression Omnibus datasets were conducted. Functional validation in OV cell lines was carried out. In total, 73 SLC family members were analyzed. Seven members were upregulated while 11 members were downregulated in OV and 15 members were protective factors for prognosis while 12 members were risk factors. SLC7A2 was downregulated in OV, and it was positively associated with prognosis. Knockdown of SLC7A2 promoted viability, invasion and migration of OV cells. These SLC family members and in particular SLC7A2 represented novel biomarkers for diagnosis and treatment for OV. | Authentic |
Text : To observe the promotion effect of Yiqi Yangxue decoction combined with chemotherapy on the rapid recovery of non-small cell lung cancer (NSCLC) patients after surgery. Eighty postoperative NSCLC patients admitted to our hospital from April 2019 to September 2021 were divided into a chemotherapy group (n = 40) and a traditional Chinese medicine (TCM) group (n = 40) according to a random sampling method. Both groups were treated with surgery and postoperative routine chemotherapy. The TCM group was treated with Yiqi Yangxue decoction, one dose per day, starting from the first day of chemotherapy. Four weeks was a course of treatment, and three courses of treatment were taken continuously. The levels of serum tumour markers (carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), carbohydrate antigen 125 (CA-125)), immune function indicators (CD3+, CD4+/CD8+, and NK cells), Pittsburgh Sleep Quality Index (PSQI) score, and Insomnia Severity Index (ISI) were compared between the two groups before and after treatment, and the clinical efficacy of the two groups was assessed with reference to the WHO efficacy criteria for solid tumours, and the toxic side effects of the two groups were assessed with reference to the WHO classification criteria for the toxic effects of chemotherapeutic drugs. After treatment, the levels of CEA, CYFRA21-1, and CA-125 were lower than those before treatment in both groups, and they were lower in the TCM group than in the chemotherapy group (P < 0.05). After treatment, the levels of CD3+, CD4+/CD8+, and NK cells in both groups were higher than before treatment, and they were higher in the TCM group than in the chemotherapy group (P < 0.05). After treatment, the PSQI and ISI scores of both the groups were lower than those before treatment, and they were higher in the TCM group than in the chemotherapy group (P < 0.05). After treatment, the overall tumour control rate was higher in the TCM group than in the chemotherapy group (P < 0.05). During the treatment period, the TCM group showed lower levels of gastrointestinal reactions, leucopenia, anaemia, and neurotoxicity than the chemotherapy group (P < 0.05). The combination of Yiqi Yangxue decoction combined with chemotherapy for postoperative NSCLC patients can effectively reduce serum tumour marker levels, enhance the body's immune function and sleep quality, and the patient's efficacy and toxicity reduction are obvious, which is conducive to the rapid recovery of many indicators after surgery. | Authentic |
Text : Colorectal cancer (CRC) is one of the most leading cancer deaths throughout the world. MiR-200c has been shown to have a critical role in cancer initiation and progression. In this study, we investigated the miR-200c expression in CRC tissues and its effects on CRC cell lines which were mediated by polycomb complex protein (BMI1). Quantitative reverse transcription polymerase chain reaction (QRT-PCR) and immunohistochemistry were used to detect miR-200c and BMI1 expression in tumor tissues from 38 patients with CRC and 38 normal colon tissues. HCT-116 and SW-48 cells were transfected by locked nucleic acid (LNA)-anti-miR-200c. Western blot analysis and real-time PCR were applied to determine the BMI1 protein and microRNA (miRNA) levels. The apoptosis was analyzed via annexin/propidium iodide staining, and cell invasion was evaluated by transwell assay. MiR-200c was markedly downregulated in CRC tissues, whereas the protein expression of BMI1 in CRC tissues was upregulated compared with normal colon tissues. In the colon cancer cell lines, transfection of LNA-anti-miR-200c increased BMI1 gene and protein expression as well as the cell invasion. Downregulation of miR-200c by LNA decreased the apoptotic cells. The results from this study revealed that miR-200c may have antitumor effects through inhibition of BMI1 expression. | Authentic |
Text : Eukaryotic elongation factor-2 kinase (eEF2K), an atypical member of alpha-kinase family, is highly overexpressed in breast, pancreatic, brain, and lung cancers, and associated with poor survival in patients. eEF2K promotes cell proliferation, survival, and aggressive tumor characteristics, leading to tumor growth and progression. While initial studies indicated that eEF2K acts as a negative regulator of protein synthesis by suppressing peptide elongation phase, later studies demonstrated that it has multiple functions and promotes cell cycle, angiogenesis, migration, and invasion as well as induction of epithelial-mesenchymal transition through induction of integrin β1, SRC/FAK, PI3K/AKT, cyclin D1, VEGF, ZEB1, Snail, and MMP-2. Under stress conditions such as hypoxia and metabolic distress, eEF2K is activated by several signaling pathways and slows down protein synthesis and helping cells to save energy and survive. In vivo therapeutic targeting of eEF2K by genetic methods inhibits tumor growth in various tumor models, validating it as a potential molecular target. Recent studies suggest that eEF2K plays a role in tumor microenvironment cells by monocyte chemoattractant protein-1 (MCP-1) and accumulation of tumor-associated macrophages. Due to its clinical significance and the pivotal role in tumorigenesis and progression, eEF2K is considered as an important therapeutic target in solid tumors. However, currently, there is no specific and potent inhibitor for translation into clinical studies. Here, we aim to systematically review current knowledge regarding eEF2K in tumor biology, microenvironment, and development of eEF2K targeted inhibitors and therapeutics. | Authentic |
Text : Accurate lung tumor identification is crucial for radiation treatment planning. Due to the low contrast of the lung tumor in computed tomography (CT) images, segmentation of the tumor in CT images is challenging. This paper effectively integrates the U-Net with the channel attention module (CAM) to segment the malignant lung area from the surrounding chest region. The SegChaNet method encodes CT slices of the input lung into feature maps utilizing the trail of encoders. Finally, we explicitly developed a multiscale, dense-feature extraction module to extract multiscale features from the collection of encoded feature maps. We have identified the segmentation map of the lungs by employing the decoders and compared SegChaNet with the state-of-the-art. The model has learned the dense-feature extraction in lung abnormalities, while iterative downsampling followed by iterative upsampling causes the network to remain invariant to the size of the dense abnormality. Experimental results show that the proposed method is accurate and efficient and directly provides explicit lung regions in complex circumstances without postprocessing. | Authentic |
Text : Penile cancer is one of the most aggressive male tumors. Although it is preventable, the main etiologic causes are lifestyle behaviors and viral infection, such as human papillomavirus (HPV). Long-term epigenetic changes due to environmental factors change cell fate and promote carcinogenesis, being an important marker of prognosis. We evaluated epidemiological aspects of penile squamous cell carcinoma (SCC) and the prevalence of HPV infection using high-risk HPV (hrHPV) and p16INK4A expression of 224 participants. Global DNA methylation was evaluated through 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). The incidence of HPV was 53.2% for hrHPV and 22.32% for p16INK4a. hrHPV was not related to systemic or lymph node metastasis and locoregional recurrence, nor influenced the survival rate. P16INK4a seems to be a protective factor for death, which does not affect metastasis or tumor recurrence. Lymph node and systemic metastases and locoregional recurrence increase the risk of death. An increased 5mC mark was observed in penile SCC regardless of HPV infection. However, there is a reduction of the 5hmC mark for p16INK4a + (P = 0.024). Increased 5mC/5hmC ratio (> 1) was observed in 94.2% of penile SCC, irrespective of HPV infection. Despite the increase in 5mC, it seems not to affect the survival rate (HR = 1.06; 95% CI 0.33-3.38). P16INK4a seems to be a good prognosis marker for penile SCC and the increase in 5mC, an epigenetic mark of genomic stability, may support tumor progression leading to poor prognosis. | Authentic |
Text : The aim of the present study was to analyze the lung targeting potential of surface engineered mesospheres loaded with doxorubicin hydrochloride (DOX). Gelatin-based DOX encapsulated mesospheres were prepared using a steric stabilization process and surface modified with mannose, using the amino group present on the surface of the mesospheres. Gelatin-DOX-mesospheres (M1) and gelatin-mannosylated-DOX-mesospheres (M2) were characterized for particle size, polydispersity index, zeta potential, and % entrapment efficiency which were found respectively 8.7 ± 0.35, 0.671 ± 0.018, 1.74 ± 0.27, and 80.4 ± 1.2 for (M1) and 9.8 ± 0.41, 0.625 ± 0.010, 0.85 ± 0.11, and 75.1 ± 0.7 for (M2). Furthermore, the mesospheres were characterized by FTIR, DSC, SEM, and TEM. In vitro drug release study of optimized formulation was carried out using the dialysis tube method. The cumulative percent drug release was found to be 79.2 ± 0.1% and 69.6 ± 0.52% respectively for gelatin-DOX-mesospheres and gelatin-mannosylated-DOX-mesospheres. In vitro cytotoxicity of formulations was determined using xenograft A-549 tumor cell lines. The cytotoxicity recorded as IC50 was more in the case of M2 compared to M1. In addition, mesospheres exhibited minimal hemolytic toxicity and appear to be promising for sustained drug delivery of DOX to the lungs. Cytotoxicity assay was conducted on the A-549 cell line. The results revealed that gelatin-mannosylated-DOX-mesospheres were maximally cytotoxic as compared to free DOX as well as gelatin-DOX-mesospheres. The lung's accumulation of drug was measured and found maximum after administration of M2. It may, therefore, be inferred that gelatin-mannosylated-DOX-mesospheres are capable to carry bioactive(s) and can be used specifically to target the lung cancer with minimal side effects. | Authentic |
Text : Our previous report described how postoperative progression of sarcopenia predicted long-term prognosis after complete resection of non-small cell lung cancer (NSCLC) in heavy smokers. However, there are currently no effective means to treat progressive sarcopenia. In this study, we aimed to confirm our previous findings in a larger population and to identify factors associated with postoperative progression of sarcopenia to propose possible preventative measures. This retrospective study analyzed the data of 1,095 patients who underwent curative lobar resection for NSCLC at Kanagawa Cancer Center. We divided patients into four groups according to sex and Brinkman index (BI) above or below 600. Six-month postoperative changes in the skeletal muscle index (SMI) were calculated and associations between clinicopathological factors including changes in SMI and mortality from postoperative 6 months were examined. Only in groups in which postoperative depletion of SMI was shown to be associated with the prognosis, we identified clinicopathological factors associated with depletive SMI. The overall survival rates of 1,095 patients were 89.8% and 82.5% at 3 and 5 years, respectively. The median 6-month change in SMI was -3.4% (range, -22.3% to +17.9%). Multivariate analysis revealed that poor prognosis was independently predicted by a large reduction in the SMI (cut-off value: -10%) in males with a BI ≥600. In 391 heavy-smoking males, factors associated with a postoperative change in SMI ≤-10% were history of other cancers (including gastric cancer) low forced expiratory volume in one second (FEV 1.0, cut-off value: 1,870 mL), and prolonged operation time (cut-off value: 200 minutes). Perioperative measures to prevent postoperative sarcopenia are appropriate for heavy smokers. We obtained some clues regarding countermeasures, one of which may be avoiding long-time operation. Further studies including clinical trials to assess perioperative anti-sarcopenia treatments, are needed. | Authentic |
Text : Long non-coding RNAs (lncRNAs) act as a member of competing endogenous RNAs (ceRNAs) and plays a significant role in tumorigenesis. The aim of this study was to identify potential lncRNA biomarkers for predicting the prognosis of lung squamous cell carcinoma (LUSC) using a comprehensive analysis of lncRNA mediated ceRNA network. Differentially expressed RNAs datasets were obtained using edge R package in 502 LUSC tissues and 49 adjacent non-LUSC tissues from the Cancer Genome Atlas (TCGA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to identify functional enrichment implication of lncRNA related differentially expressed mRNAs. Survival analysis was used Kaplan-Meier curve method. Univariate and multivariate Cox regression analysis were performed to construct a predictive model with lncRNA biomarkers. A total of 2185 lncRNAs, 170 miRNAs and 2053 mRNAs were differentially expressed between LUSC tissues and adjacent non-LUSC tissues. The novel constructed ceRNA network incorporated 184 LUSC-specific lncRNAs, 18 miRNAs, and 49 mRNAs. About 11 of 184 differentially expressed lncRNAs and 1 of 18 differentially expressed miRNAs and 5 of 49 differentially expressed mRNAs were conspicuously related to overall survival (p < .05). Univariate and multivariate cox regression analysis showed that 6 lncRNAs were retrieved to construct a predictive model to predict the overall survival in LUSC patients. In conclusion, CeRNAs contributed to the progression of LUSC and a model with 6 lncRNAs might be potential biomarker for predicting the prognosis of LUSC. | Authentic |
Text : Multiple myeloma (MM) cells gain protection against drugs through interaction with bone marrow stromal cells (BMSCs). This form of resistance largely accounts for resistance to therapy in MM patients which warrants further exploration to identify more potential therapeutic targets. We performed miRNA/mRNA qPCR arrays and western blotting to analyze transcriptional and translational changes in MM cells co-cultured with BMSCs. Drug cytotoxicity and apoptosis in MMGFP-BMSC co-cultures were measured using fluorescence plate reader and flowcytometry, respectively. miRNA was overexpressed in MM cell lines using Lentiviral transduction, miRNA-3'UTR binding was examined using luciferase assay. We found that BMSCs downregulated miR-101-3p and upregulated survivin (BIRC5) in MM cells. Survivin was downregulated by miR-101-3p overexpression and found to be a direct target of miR-101-3p using 3'UTR luciferase assay. Overexpression of survivin increased viability of MM cells in the presence of anti-myeloma drugs, and miR-101-3p inhibition by anti-miR against miR-101-3p upregulated survivin. Furthermore, overexpression of miR-101-3p or silencing of survivin triggered apoptosis in MM cells and sensitized them to anti-myeloma drugs in the presence of BMSCs overcoming the stroma-induced drug resistance. Our study demonstrates that BMSC-induced resistance to drugs is associated with survivin upregulation which is a direct target of miR-101-3p. This study also identifies miR-101-3p-survivin interaction as a druggable target involved in stroma-mediated drug resistance in MM and suggests it for developing more efficient therapeutic strategies. | Authentic |
Text : Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors. Studies have indicated that long noncoding RNAs (lncRNAs) function as important regulators in progression of tumorigenesis. In this study, lncRNA small nucleolar RNA host gene 7 (SNHG7) was selected to identify how it functioned in the development of NPC. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to detect SNHG7 expression in paired NPC patient tissue samples and cell lines. The role of SNHG7 in the metastasis of NPC was detected through scratch wound assay and Transwell assay. RT-qPCR and western blot assay were used to discover the function of SNHG7 in epithelial-to-mesenchymal transition (EMT) process. Tumor metastasis assay was also performed in vivo. In this study, RT-qPCR results showed that SNHG7 expression in NPC samples was remarkably higher when compared with that in adjacent ones. Cell invasion and cell migration of NPC were inhibited due to silence of SNHG7 and were promoted due to overexpression of SNHG7. Moreover, results of further experiments revealed that the EMT-related proteins were regulated via knockdown or overexpression of SNHG7 in NPC. Furthermore, tumor metastasis of NPC was inhibited via knockdown of SNHG7 and was enhanced via overexpression of SNHG7 in nude mice. These results indicate that SNHG7 enhances NPC cell invasion and cell migration by eliciting the EMT process. | Counterfeit |
Text : The advent of nanoparticles revolutionised the drug delivery systems in human diseases; however, their prominent role was highlighted in the cancer-based therapies, where this technology could specifically target cancer cells. Herein, we decided to combine two nanoparticles Fe3O4 and ZnO to fabricate a new anti-cancer nanocomposite. Noteworthy, hydroxylated carbon nanotube (CNT) was used to increase the water-solubility of the compound, improving its uptake by malignant cells. This study was designed to evaluate the anticancer property as well as the molecular mechanisms of ZnO/CNT@Fe3O4 nanocomposite cytotoxicity in CML-derived K562 cells. Our results outlined that ZnO/CNT@Fe3O4 decreased the proliferative capacity of K562 cells through induction of G1 arrest and induced apoptosis probably via ROS-dependent upregulation of FOXO3a and SIRT1. The results of qRT-PCR analysis also demonstrated that while ZnO/CNT@Fe3O4 significantly increased the expression of pro-apoptotic genes in K562 cells, it had no significant inhibitory effect on the expression levels of anti-apoptotic target genes of NF-κB; proposing an attenuating role of NF-κB signalling pathway in K562 cell response to ZnO/CNT@Fe3O4. Synergistic experiment showed that ZnO/CNT@Fe3O4 could enhance the cytotoxic effects of imatinib on K562 cells. Overall, it seems that pharmaceutical application of nanocomposites possesses novel promising potential for leukaemia treatment strategies. | Authentic |
Text : Type 1 and 2 diabetes confer an increased risk of pancreatic cancer (PaC) of similar magnitude, suggesting a common mechanism. The recent finding that PaC incidence increases linearly with increasing fasting glucose levels supports a central role for hyperglycaemia, which is known to cause carbonyl stress and advanced glycation end-product (AGE) accumulation through increased glycolytic activity and non-enzymatic reactions. This study investigated the impact of hyperglycaemia on invasive tumour development and the underlying mechanisms involved. Pdx1-Cre;LSL-KrasG12D/+ mice were interbred with mitosis luciferase reporter mice, rendered diabetic with streptozotocin and treated or not with carnosinol (FL-926-16), a selective scavenger of reactive carbonyl species (RCS) and, as such, an inhibitor of AGE formation. Mice were monitored for tumour development by in vivo bioluminescence imaging. At the end of the study, pancreatic tissue was collected for histology/immunohistochemistry and molecular analyses. Mechanistic studies were performed in pancreatic ductal adenocarcinoma cell lines challenged with high glucose, glycolysis- and glycoxidation-derived RCS, their protein adducts AGEs and sera from diabetic patients. Cumulative incidence of invasive PaC at 22 weeks of age was 75% in untreated diabetic vs 25% in FL-926-16-gtreated diabetic and 8.3% in non-diabetic mice. FL-926-16 treatment suppressed systemic and pancreatic carbonyl stress, extracellular signal-regulated kinases (ERK) 1/2 activation, and nuclear translocation of Yes-associated protein (YAP) in pancreas. In vitro, RCS scavenging and AGE elimination completely inhibited cell proliferation stimulated by high glucose, and YAP proved essential in mediating the effects of both glucose-derived RCS and their protein adducts AGEs. However, RCS and AGEs induced YAP activity through distinct pathways, causing reduction of Large Tumour Suppressor Kinase 1 and activation of the Epidermal Growth Factor Receptor/ERK signalling pathway, respectively. An RCS scavenger and AGE inhibitor prevented the accelerating effect of diabetes on PainINs progression to invasive PaC, showing that hyperglycaemia promotes PaC mainly through increased carbonyl stress. In vitro experiments demonstrated that both circulating RCS/AGEs and tumour cell-derived carbonyl stress generated by excess glucose metabolism induce proliferation by YAP activation, hence providing a molecular mechanism underlying the link between diabetes and PaC (and cancer in general). | Authentic |
Text : Tumor suppressor long noncoding RNA maternally expressed gene 3 (lncRNA MEG3) exists in various cancers. Nonetheless, the functions of lncRNA MEG3 in choriocarcinoma (CC) are still not well studied. We explored the effects of lncRNA MEG3 on human CC JEG-3 and BeWo cells. lncRNA MEG3 was overexpressed, and the effects of lncRNA MEG3 on cell viability, proliferation, apoptosis, migration, and invasion were assessed by the cell counting kit-8 assay, western blot analysis, flow cytometry (plus western blot analysis), and transwell assay (plus western blot analysis), respectively. Then, the expression level of miR-211 was detected by real-time quantitative polymerase chain reaction. After that, the effects of dysregulated microRNA-211 (miR-211) with overexpressing lncRNA MEG3 on JEG-3 cells and BeWo cells were testified. Western blot analysis was used to study the involvements of the signaling pathways in the lncRNA MEG3-associated modulation. We found that lncRNA MEG3 upregulation reduced cell viability, inhibited proliferation, migration and invasion, and promoted apoptosis. Expression of miR-211 was upregulated after lncRNA MEG3 overexpression. Effects of lncRNA MEG3 overexpression were augmented by miR-211 overexpression, while they were declined by miR-211 silencing. Phosphorylated levels of PI3K, AKT, and AMP-activated protein kinase (AMPK) were decreased by lncRNA MEG3 overexpression via regulation of miR-211. To sum up, lncRNA MEG3 could repress proliferation, migration and invasion, and promote apoptosis of JEG-3 and BeWo cells through upregulating miR-211. The PI3K/AKT and AMPK pathways were inhibited by lncRNA MEG3 overexpression via regulation of miR-211. | Counterfeit |
Text : To explore the influences of propofol on the proliferation and apoptosis of cardia cancer cells via mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway. A total of 65 surgical resection specimens of cardia cancer were selected as research objects and divided into control group and with low (12.5 μmol/L), medium (25 μmol/L), and high (50 μmol/L) propofol concentration groups. The apoptosis of cancer cells, ERK1/2 phosphorylation level, expressions of Caspase-3, B-cell lymphoma-2 (Bcl-2), and Bcl-2 associated X protein (Bax) in each group were detected. Propofol in different concentrations could all effectively inhibit the proliferation of cardia cancer cells in a dose-dependent manner. Different concentrations of propofol promoted the apoptosis of cardia cancer cells, and the apoptosis rate constantly increased with the rising concentration of propofol (p<0.05). Propofol could repress the expression of Bcl-2 and up-regulate the expression levels of Caspase-3, Bax, and phosphorylated ERK1/2. Propofol can inhibit the proliferation and induce the apoptosis of cardia cancer cells, and the action mechanism may be correlated with the inhibition on the MAPK/ERK signaling pathway. | Authentic |
Text : MicroRNA-874 (miR-874) is downregulated and acts as a tumor suppressor in several types of cancers, whereas the biological function of miR-874 in colorectal cancer (CRC) remains unclear. The aims of the present study were to investigate the clinical significance, biological effects, and the underlying mechanisms of miR-874 in CRC. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect miR-874 expression in CRC cell lines and tissue samples. MTT and colony formation assays and flow cytometry were performed to analyze the effects of miR-874 expression on growth, apoptosis and the chemoresistance of CRC cells. Regulation of putative miR-874 targets was determined by dual-luciferase reporter assays. RT-qPCR and western blot assays were performed to detected the levels of X-linked inhibitor of apoptosis protein (XIAP) mRNA and protein expression. It was found that expression of miR-874 was downregulated in CRC tissues and cell lines, and its expression was significantly negatively correlated with TNM stage and lymph node metastasis of the CRC patients. Functional assays revealed that restoration of miR-874 inhibited proliferation, reduced colony formation, enhanced apoptosis, as well as decreased the 5-fluorouracil (5-FU) resistance of the CRC cells. Through luciferase activity assay, RT-qPCR and western blot analysis, XIAP was shown to be a direct target of miR-874. In addition, XIAP expression was significantly increased in the CRC tissues and cell lines, and was inversely correlated with miR-874 expression. Importantly, downregulation of XIAP in CRC cells had an effect similar to that of miR-874 overexpression. Taken together, these data showed that miR-874 inhibits growth, increases apoptosis and enhances chemosensitivity in CRC cells by targeting XIAP, suggesting that miR-874 may be a potential molecular target for the treatment of human CRC. | Counterfeit |
Text : In this study, carbon dots synthesized from bamboo leaf cellulose were used simultaneously as a staining agent and for doxorubicin delivery to target cancer cells. Owing to their nontoxic properties, the production of carbon dots from bamboo leaves is a green approach involving optimized application of bamboo tree waste. For multifunctional applications, the carbon dots were modified with 4-carboxybenzylboronic acid and doxorubicin to improve target specificity and drug delivery to HeLa tumor cells. The resulting modified carbon dots were characterized using different analytical techniques, which showed that they were biocompatible, nontoxic, and highly stable over a wide range of pH values and at high ionic strengths. Furthermore, in vitro confocal microscopy studies demonstrated their blue fluorescence and cellular pathway for entering HeLa cells via folate receptor-mediated endocytosis. Cell viability data and flow cytometry results also confirmed the selective uptake of the carbon dots by HeLa cells, which significantly enhanced cell cytotoxicity. | Authentic |
Text : Malignant cancers are distinguished from more benign forms of cancers by enhanced ability to disseminate. A number of factors aid the migration and invasion of malignant cancer cells. Epithelial-to-mesenchymal transition (EMT), which greatly facilitates the dissemination of cancer cells, is characterized by the loss of epithelial markers and the acquisition of mesenchymal markers thereby rendering the cells more migratory and invasive. We have previously shown that the class III lysine deacetylase SIRT1 plays a critical role curbing the metastasis of ovarian cancer cells partly by blocking EMT. Here we investigated the mechanism by which SIRT1 regulates the transcription of Claudin 5 (CLDN5), an epithelial marker gene, in ovarian cancer cells. SIRT1 activation or over-expression up-regulated CLDN5 expression while SIRT1 inhibition or depletion down-regulated CLDN5 expression. SIRT1 interacted with and deacetylated Kruppel-like factor 4 (KLF4), a known transcriptional activator for CLDN5. Deacetylation by SIRT1 promoted nuclear accumulation of KLF4 and enhanced the binding of KLF4 to the CLDN5 promoter in the nucleus. SIRT1-mediated up-regulation of CLDN5 was abrogated in the absence of KLF4. In accordance, KLF4 depletion by siRNA rendered ovarian cancer cells more migratory and invasive despite of SIRT1 activation or over-expression. In conclusion, our data suggest that SIRT1 activates CLDN5 transcription by deacetylating and potentiating KLF4. | Authentic |
Text : Testicular germ cell tumors (TGCTs) are generally rare but represent the most common solid tumors in young men. They are classified broadly into seminoma, which resemble primordial germ cells (PGCs), and non-seminoma, which are either undifferentiated (embryonic carcinoma) or differentiated (teratoma, yolk sac tumor, choriocarcinomas) patterning. A widespread role for microRNAs (miRNAs), in diverse molecular processes driving initiation and progression of various types of TGCTs has been recently studied. We discuss the involvement of different miRNAs in the development and progression of different types of TGCTs. Moreover, we highlight the aberrant expression of miRNAs in TGCTs and several targets, which may define miRNAs as oncomiRs or tumor suppressors. A better understanding of miRNA biology may ultimately yield further insight into the molecular mechanisms of tumorigenesis and new therapeutic strategies against TGCTs. | Authentic |
Text : Emerging evidence demonstrates that competing endogenous RNA (ceRNA) hypothesis has played a role in molecular biological mechanisms of cancer occurrence and development. But the effect of ceRNA network in bladder cancer (BC), especially lncRNA-miRNA-mRNA regulatory network of BC, was not completely expounded. By means of The Cancer Genome Atlas (TCGA) database, we compared the expression of RNA sequencing (RNA-Seq) data between 19 normal bladder tissue and 414 primary bladder tumours. Then, weighted gene co-expression network analysis (WGCNA) was conducted to analyse the correlation between two sets of genes with traits. Interactions between miRNAs, lncRNAs and target mRNAs were predicted by MiRcode, miRDB, starBase, miRTarBase and TargetScan. Next, by univariate Cox regression and LASSO regression analysis, the 86 mRNAs obtained by prediction were used to construct a prognostic model which contained 4 mRNAs (ACTC1 + FAM129A + OSBPL10 + EPHA2). Then, by the 4 mRNAs in the prognostic model, a ceRNA regulatory network with 48 lncRNAs, 14 miRNAs and 4 mRNAs was constructed. To sum up, the ceRNA network can further explore gene regulation and predict the prognosis of BC patients. | Authentic |
Text : Thyroid cancer is a frequently happened malignancy in human endocrine system. Papillary thyroid cancer (PTC) presents 70-80% of all thyroid cancer cases. Herein, we probed the possible oncogenic function of long non-coding RNA (lncRNA) highly up-regulated in liver cancer (HULC) in PTC. First, the HULC and microRNA-106a (miR-106a) expressions in PTC tissues and cells were tested. Plasmids or miRNAs transfections were done for altering HULC and miR-106a expressions. Then, cells viability and apoptosis, along with cell proliferative, migratory and invasive abilities, were tested, respectively. The PI3K/AKT and Wnt/β-catenin pathways activities were measured. Finally, the animal model of PTC was constructed and the tumour volumes and weights were gauged. We discovered that HULC and miR-106a had relative high expression levels in PTC tissues and cells. HULC overexpression enhanced TPC-1 cells viability and cell proliferative, migratory and invasive abilities. Silencing HULC induced TPC-1 cell apoptosis. miR-106a engaged in the oncogenic impacts of HULC. Moreover, HULC overexpression boosted PI3K/AKT and Wnt/β-catenin pathways activities via raising miR-106a expression. Besides, HULC overexpression enhanced the volumes and weights of PTC tumours. To sum up, HULC exhibited oncogenic function on PTC in vitro and in vivo. | Authentic |
Text : Syndecan-1 (SDC-1) is a crucial membrane proteoglycan, which is confirmed to participate in several tumor cell biological processes. However, the biological significance of SDC-1 in colorectal carcinoma is not yet clear. An objective of this study was to investigate the role of SDC-1 in colorectal carcinoma cells. Expression of SDC-1 in colorectal carcinoma tissues was evaluated by Reverse transcription-quantitative real-time PCR (RT-qPCR) and western blot. After transfection with pcDNA3.1 or pc-SDC-1, the transfection efficiency was measured. Next, SW480, SW620 and LOVO cell viability, apoptosis, migration and adhesion were assessed to explore the effects of exogenous overexpressed SDC-1 on colorectal carcinoma. In addition, the influences of aberrant expressed SDC-1 in Janus kinase 1 (JAK1)/signal transducer and activator of transcription 3 (STAT3) and rat sarcoma virus (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways were detected by western blot analysis. SDC-1 mRNA and protein levels were down-regulated in human colorectal carcinoma tissues. SDC-1 overexpression inhibited cell proliferation via suppressing CyclinD1 and c-Myc expression, meanwhile stimulated cell apoptosis via increasing the expression levels of B-cell lymphoma-2-associated x (Bax) and Cleaved-Caspase-3. Additionally, SDC-1 overexpression restrained cell migration via inhibiting the protein expression of matrix metallopeptidase 9 (MMP-9), and elicited cell adhesion through increasing intercellular cell adhesion molecule-1 (ICAM-1). Furthermore, SDC-1 overexpression suppressed JAK1/STAT3 and Ras/Raf/MEK/ERK-related protein levels. In general, the evidence from this study suggested that SDC-1 suppressed cell growth, migration through blocking JAK1/STAT3 and Ras/Raf/MEK/ERK pathways in human colorectal carcinoma cells. | Counterfeit |
Text : Resistance to medications is one of the main complications in chemotherapy of cancer. It has been shown that some multidrug resistant cancer cells indicate more sensitivity against cytotoxic effects of TNF-α compared to their parental cells. Our previous findings indicated vulnerability of the mitoxantrone-resistant breast cancer cells MCF-7/MX to cell death induced by TNF-α compared to the parent cells MCF-7. In this study, we performed a comparative proteomics analysis for identification of proteins involved in induction of higher susceptibility of MCF-7/MX cells to cytotoxic effect of TNF-α. Intensity of protein spots in 2D gel electrophoresis profiles of MCF-7 and MCF-7/MX cells were compared with Image Master Platinum 6.0 software. Selected differential protein-spots were identified with MALDI-TOF/TOF mass spectrometry and database searching. Pathway analyses of identified proteins were performed using PANTHER, KEGG PATHWAY, Gene MANIA and STRING databases. Western blot was performed for confirmation of the proteomics results. Our results indicated that 48 hr exposure to TNF-α induced 87% death in MCF-7/MX cells compared to 19% death in MCF-7 cells. Forty landmarks per 2D gel electrophoresis were matched by Image Master Software. Six proteins were identified with mass spectrometry. Western blot showed that 14-3-3γ and p53 proteins were expressed higher in MCF-7/MX cells treated with TNF-α compared to MCF-7 cells treated with TNF-α. Our results showed that 14-3-3 γ, prohibitin, peroxiredoxin 2 and P53 proteins which were expressed differentially in MCF-7/MX cells treated with TNF-α may involve in the induction of higher rates of cell death in these cells compared to TNF-α-treated MCF-7 cells. | Authentic |
Text : Proteomic analysis of extracellular vesicles (EVs) from biological fluid is a powerful approach to discover potential biomarkers for human diseases including cancers, as EV secreted to biological fluids are originated from the affected tissue. In order to investigate significant molecules related to the pathogenesis of bladder cancer, EVs were isolated from patient urine which was analyzed by mass spectrometry based proteomics. Comparison of the EV proteome to the whole urine proteome demonstrated an increased number of protein identification in EV. Comparative MS analyses of urinary EV from control subjects and bladder cancer patients identified a total of 1,222 proteins. Statistical analyses provided 56 proteins significantly increased in bladder cancer urine, including proteins for which expression levels varied by cancer stage (P-value < 0.05). While urine represents a valuable, noninvasive specimen for biomarker discovery in urologic cancers, there is a high degree of intra- and inter-individual variability in urine samples. The enrichment of urinary EV demonstrated its capability and applicability of providing a focused identification of biologically relevant proteins in urological diseases. | Authentic |
Text : Osteoblast has been found to exert indispensable functions during fracture healing. This study aimed to investigate the effects of kaempferol, a natural flavonoid compound, on osteoblast proliferation, migration and differentiation, as well as possible molecular mechanisms. qRT-PCR was performed to measure the expression level of microRNA-101 (miR-101). Cell viability and migration were respectively assessed using cell counting kit-8 (CCK-8) assay and two-chamber migration assay. Relative alkaline phosphatase (ALP) activity was evaluated using p-nitrophenyl phosphate (pNPP) as substrate. Western blotting was used to detect the protein expression levels of key molecules involved in cell proliferation, migration, differentiation, and Wnt/β-catenin pathway. Kaempferol treatment significantly promoted MC3T3-E1 cell proliferation, migration, and differentiation. Mechanistically, kaempferol notably enhanced the expression level of miR-101 in MC3T3-E1 cells. Knockdown of miR-101 obviously weakened the promoting effects of kaempferol on MC3T3-E1 cell proliferation, migration, and differentiation. In addition, kaempferol remarkably activated Wnt/β-catenin pathway in MC3T3-E1 cells via up-regulating miR-101. This research further confirmed the promoting effects of kaempferol on osteoblast proliferation, migration, and differentiation. The up-regulation of miR-101 and activation of Wnt/β-catenin pathway caused by kaempferol play critical roles in the promoting effects of kaempferol on osteoblast proliferation, migration, and differentiation. | Counterfeit |
Text : Origanum vulgare essential oil (EO) is traditionally well-known for its aromatic properties and biomedical applications, including anticancer. This was the first report where oregano essential oil-based nano emulsion (OENE) was synthesized for studying its effects on prostate cancer cell lines (PC3). At first, we have synthesized OENE and characterized using various spectroscopic analyses. The toxicity and inhibitory concentration (IC50) of OENE toward prostate cancer by MTT analysis were performed. The lipid biogenesis mediated, molecular target pathway analyses were performed using fluorescence cellular staining techniques, real-time RT-PCR, or western blotting analysis. OENE showed IC50 at 13.82 µg/mL and significantly induced distinct morphological changes, including cell shrinkage, cell density, and cell shape reduction. In addition, OENE could also significantly decreased lipid droplet accumulation which was confirmed by studying mRNA transcripts of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) (0.31-fold), fatty acid synthase (FASN) (0.18-fold), and sterol regulatory element-binding protein (SREPB1) (0.11-fold), respectively. Furthermore, there is a significant upregulation BAX (BCL2 associated X) and caspase 3 expressions. Nevertheless, OENE decreased the transcript level of BCL2 (B-cell lymphoma 2), thus resulting in apoptosis. Overall, our present work demonstrated that OENE could be a therapeutic target for the treatment of prostate cancer and warrants in vivo studies. | Authentic |
Text : Most hepatocellular carcinomas (HCCs) arise in the context of chronic liver disease and/or cirrhosis. Thus, chemoprevention in individuals at risk represents an important but yet unproven approach. In this study, we investigated the ability of microRNA (miRNA)-based molecules to prevent liver cancer development in a cirrhotic model. To this end, we developed a mouse model able to recapitulate the natural progression from fibrosis to HCC, and then we tested the prophylactic activity of an miRNA-based approach in the model. The experiments were carried out in the TG221 transgenic mouse, characterized by the overexpression of miR-221 in the liver and predisposed to the development of liver tumors. TG221 as well as wild-type mice were exposed to the hepatotoxin carbon tetrachloride (CCl4) to induce chronic liver damage. All mice developed liver cirrhosis, but only TG221 mice developed nodular lesions in 100% of cases within 6 months of age. The spectrum of lesions ranged from dysplastic foci to carcinomas. To investigate miRNA-based prophylactic approaches, anti-miR-221 oligonucleotides or miR-199a-3p mimics were administered to TG221 CCl4-treated mice. Compared to control animals, a significant reduction in number, size, and, most significantly, malignant phenotype of liver nodules was observed, thus demonstrating an important prophylactic action of miRNA-based molecules. In summary, in this article, we not only report a simple model of liver cancer in a cirrhotic background but also provide evidence for a potential miRNA-based approach to reduce the risk of HCC development. | Authentic |
Text : Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer-related death in women globally. Its high morbidity and mortality, as well as its elevated tendency to metastasize to other organs, warrant the urgency to find new biomarkers for breast cancer diagnosis and treatment. The specific roles of long noncoding RNA linc-ITGB1 on cell proliferation and metastasis in breast cancer were explored in this study. The expression of linc-ITGB1 was significantly upregulated in both clinical breast cancer tissues and cultured breast cancer cell lines. The linc-ITGB1 knockdown with specific short hairpin RNA (shRNA) decreased cell proliferation and colony formation in vitro. Tumor growth in vivo was also inhibited by linc-ITGB1 depletion. In addition, linc-ITGB1 depletion caused cell accumulation in the G0/G1 phase. Breast cancer cell lines with linc-ITGB1 depletion exhibited decreased migration and invasion abilities compared with the control cells. Furthermore, the linc-ITGB1 knockdown decreased the expression of mesenchymal markers N-cadherin and vimentin while increasing the expression of the epithelial marker E-cadherin. Key cell cycle regulators Cdc25C and Cyclin B1 were also decreased by the linc-ITGB1 knockdown. These data suggest that linc-ITGB1 promotes breast cancer progression by inducing cell cycle arrest and interrupting the epithelial-to-mesenchymal transition process. | Authentic |
Text : Myocardial dysfunction is an important manifestation of sepsis. In addition, inactivation of the mitogen-activated protein kinase (MAPK) signaling pathway has been reported to be beneficial in sepsis. The current study used gene expression profiling to demonstrate the overexpression of angiotensin II type 1 receptor (AT1R) and activation of the MAPK signaling pathway in sepsis. In this study, we used a rat model of sepsis established by cecal ligation and puncture to explore the mechanism of AT1R silencing in relation to the MAPK signaling pathway on myocardial injury. Various parameters including blood pressure, heart rate, and cardiac function changes were observed. Enzyme-linked immunosorbent assay was used to measure the concentration of cardiac troponin T (TnT), cardiac troponin I (cTnI), and creatine kinase isoenzyme muscle/brain (CK-MB). Myocardial enzyme, tissue antioxidant capacity, mitochondria swelling, and membrane potential were also detected. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling staining was applied to measure cell apoptosis, and messenger RNA and protein levels of apoptosis-related proteins (Fas ligand [Fasl], B-cell CLL/lymphoma [Bcl-2], p53) were also detected. Initially, sepsis rats exhibited decreased survival rate, but increased ejection fraction (EF), heart rate, and concentrations of TnT, cTnI, and CK-MB. Furthermore, decreased AT1R expression inactivated the MAPK signaling pathway (shown as decreased extracellular signal-regulated kinase and cyclic adenosine 3',5'-monophosphate response element binding protein expression), decreased EF, heart rate, and concentrations of TnT, cTnI, and CK-MB, but increased sepsis rat survival rate. Eventually, decreased AT1R expression inhibited myocardial cell apoptosis (shown as decreased apoptosis rate and p53 and Fasl expression as well as increased Bcl-2 expression). These findings indicated that AT1R silencing plays an inhibitory role in sepsis-induced myocardial injury by inhibiting the MAPK signaling pathway. | Counterfeit |
Text : Breast cancer is a common malignant tumor among women whose prognosis is largely determined by the period and accuracy of diagnosis. We here propose to identify a robust DNA methylation-based breast cancer-specific diagnostic signature. Genome-wide DNA methylation and gene expression profiles of breast cancer patients along with their adjacent normal tissues from the Cancer Genome Atlas (TCGA) were obtained as the training set. CpGs that with significantly elevated methylation level in breast cancer than not only their adjacent normal tissues and the other ten common cancers from TCGA but also the healthy breast tissues from the Gene Expression Omnibus (GEO) were finally remained for logistic regression analysis. Another independent breast cancer DNA methylation dataset from GEO was used as the testing set. Lots of CpGs were hyper-methylated in breast cancer samples compared with adjacent normal tissues, which tend to be negatively correlated with gene expressions. Eight CpGs located at RIIAD1, ENPP2, ESPN, and ETS1, were finally retained. The diagnostic model was reliable in separating BRCA from normal samples. Besides, chromatin accessibility status of RIIAD1, ENPP2, ESPN and ETS1 showed great differences between MCF-7 and MDA-MB-231 cell lines. In conclusion, the present study should be helpful for breast cancer early and accurate diagnosis. | Authentic |
Text : To investigate the technical feasibility of using ultrasound-guided intratumoral radiofrequency hyperthermia (RFH) to enhance local chemotherapy of rat orthotopic pancreatic cancers. Orthotopic pancreatic cancer masses were established by inoculating luciferase/mCherry labeled-pancreatic cancer cells into the pancreatic tails of Lewis model rats via a laparotomy approach. Twenty-four rats with pancreatic cancer and 24 mice with subcutaneous pancreatic cancer xenografts in four study groups (n = 6/group) received various treatments: i) combination therapy of intratumoral MR imaging-heating-guidewire-mediated RFH (42oC) plus local chemotherapy (gemcitabine); ii) intratumoral chemotherapy alone; iii) RFH alone; and (iv)phosphate-buffered saline (PBS). Transcutaneous ultrasound imaging was used to guide the treatment and subsequently follow changes in tumor sizes. Bioluminescence optical imaging was performed to follow photon signal changes. Sonographic and optical findings were correlated with histology at 14 days. Optical imaging demonstrated a significantly decreased bioluminescence signal in mice with combination therapy group, compared with the other control groups (0.51±0.18 VS 1.6±0.4 VS 3.18±0.9 VS 3.5±0.96, p < 0.05). Ultrasound imaging showed the smallest tumor volumes of both mice and rat group with the combination therapy, compared with other control groups (0.62±0.16 VS 1.25±0.19 VS 2.28±0.25 VS 2.64±0.26, p < 0.05) and (0.75±0.18 VS 1.31±0.30 VS 1.61±0.28 VS 1.72±0.28, p < 0.05). Both imaging findings were confirmed by histologic correlation. Intratumoral RFH can augment the chemotherapeutic effect in an orthotopic pancreatic cancer model. | Authentic |
Text : Eph receptors constitute the largest family of RTKs, and their associations with antitumor immunity and immunotherapy are largely unknown. By integrating genomic, transcriptomic and clinical data from cohorts in public databases, we identified EPHA5 as the most common mutated gene of Eph receptors in lung adenocarcinoma (LUAD). Moreover, compared with EPHA5 wild-type (WT) patients, EPHA5-mutant (Mut) patients exhibited significantly enhanced infiltration of CD8+ T cells and M1 macrophages, reduced recruitment of immunosuppressive regulatory T cells (Tregs) into the tumor site, as well as the increased level of chemokine, interferon-gamma, inhibitory immune checkpoint signatures, tumor mutation burden (TMB) and tumor neoantigen burden (TNB). Additionally, EPHA5 mutation cooccurred with homologous recombination (HR) or mismatch repair (MMR) gene mutations. These data were validated in the LUAD cell line H1299 and a Chinese LUAD cohort. Most importantly, clinical analysis of a Memorial Sloan Kettering Cancer Center (MSKCC) immunotherapy cohort indicated that LUAD patients with EPHA5 mutations who were treated with immunotherapy had markedly prolonged survival times. Our results revealed the correlation of EPHA5 mutations with tumor immune microenvironment and predictive factors for immunotherapy, implying the potential of EPHA5 mutations as a prognostic marker for the prognosis of LUAD patients to immune checkpoint blockade therapy. | Authentic |
Text : PD-L1 (Programmed cell death 1 ligand 1, PD-L1), an essential immune checkpoint molecule in the tumor microenvironment, is an important target for cancer immunotherapy. We have previously reported that its expression in human gastric and esophageal cancer tissues is significantly associated with cancer progression and patients' postoperative prognoses. Its expression in cancer cells is well known to inhibit the T cell-mediated anti-tumor response, and this mechanism of action has been targeted for cancer immunotherapy. As of now, the autonomous effect of PD-L1 on cancer cells is not well understood, thus our present study aimed to examine the role of PD-L1 intervention in cellular biological functions, especially epithelial to mesenchymal transition (EMT), of the human esophageal cancer cell line, Eca-109 cells. Immunohistochemistry assay was used to investigate the correlation between expression of PD-L1 and EMT markers in human esophageal cancer tissues. Intervention of PD-L1 by using RNAi and over-expression methods were used to study the role of PD-L1 in regulation of biological behaviors and EMT in Eca-109 cells. Our clinical and pathological data demonstrated that tumor samples in the EMT positive subgroup had higher PD-L1 expression than those in the EMT negative subgroup. By manipulating PD-L1 expression in Eca-109 cells either through ablation or overexpression of wild type and the cytoplasmic domain-truncated mutant, we demonstrated that PD-L1 expression significantly promoted the cell viability, migration and EMT phenotype. Furthermore, our study also indicated that PD-1 fusion protein mediated stimulation of PD-L1 and the cytoplasmic domain of PD-L1 played a critical role in promoting EMT phenotype of Eca-109 cells, thereby suggesting that PD-1 receptor usually by triggering the reverse signaling can effect PD-L1 mediated regulation of esophageal cancer cell response. Our present study reveals a tumor cell-autonomous role of PD-L1 signaling in promoting EMT in human esophageal cancer. | Authentic |
Text : To improve the analysis ability of point cloud 3D reconstruction of sparse images of nano-ceramic sculpture points, an automatic cloud 3D reconstruction method of nano-ceramic sculpture points based on sparse image sequence is proposed. Firstly, 3D angle detection and edge contour feature extraction methods are used to analyze 3D point cloud features of nano-ceramic sculpture point save image; secondly, the point cloud of the fuel economy image of nano-ceramic sculpture points is merged and the sloping action method is used to shape degradation to realize the information increase and fusion filtering of the fuel economy image of nano-ceramic sculpture points; finally, combined with the local mean denoising method, image is refined to improve the ability of sparse image outline structure of nano-ceramic sculpture points. The simulation results show that this method has high accuracy, good image matching ability, and high signal-to-noise ratio. | Counterfeit |
Text : Integrin β4 (ITGβ4) is a class of transmembrane adhesion molecules composed of hemidesmosomes (HDs). Its unique long intracellular domain provides intricate signal transduction functions. These signal transduction effects are especially prominent in tumors. Many recent studies have shown that integrin β4 is differentially expressed in various tumors, and it plays a vital role in tumor invasion, proliferation, epithelial-mesenchymal transition, and angiogenesis. Therefore, we categorize the research related to integrin β4, starting from its structure and function in tumor tissues, and provide a basic description. Based on its structure and function, we believe that integrin β4 can be used as a tumor marker. In clinical practice, it is described as a diagnostic marker for the targeted treatment of cancer and will be helpful in the clinical diagnosis and treatment of tumors. | Authentic |
Text : Many studies suggested that cytokines interleukin (IL)-29, IL-32, and tumor necrosis factor alpha (TNF-α) are implicated in the pathogenesis of malignancies. The purpose of this study was to determine the clinical significance of the serum levels of IL-29, IL-32, and TNF-α in gastric cancer (GC) patients. Fifty-eight GC patients and 20 age- and sex-matched healthy controls were enrolled into this study. The median age at diagnosis was 59.5 years (range 32-82 years). Tumor localization of the majority of the patients was antrum (n = 42, 72.4 %), and tumor histopathology of the majority of the patients was diffuse (n = 43, 74.1 %). The majority of the patients had stage IV disease (n = 41, 70.7 %). Thirty-six (62.1 %) patients had lymph node involvement. The median follow-up time was 66 months (range 1 to 97.2 months). The baseline serum IL-29 concentrations were not different between patients and controls (p = 0.627). The baseline serum IL-32 and TNF-α concentrations of the GC patients were significantly higher (for IL-32, p = 0.014; for TNF-α, p = 0.001). Gender, localization, histopathology, tumor, and lymph node involvement were not found to be correlated with serum IL-29, IL-32, and TNF-α concentrations (p > 0.05). Patients without metastasis (p = 0.01) and patients who responded to chemotherapy (p = 0.04) had higher serum IL-29 concentrations. Patients older than 60 years had higher serum IL-32 (p = 0.002). Serum IL-29, IL-32, and TNF-α levels were not associated with outcome (p = 0.30, p = 0.51, and p = 0.41, respectively). In conclusion, serum levels of IL-32 and TNF-α may be diagnostic markers, and serum IL-29 levels may be associated with good prognosis in patients with GC. | Authentic |
Text : To investigate the role of zinc finger E‑box‑binding homeobox 2 antisense RNA 1 (ZEB2-AS1) in regulating laryngeal squamous cell carcinoma (LSCC) progression. In this retrospective study, we included all patients who underwent a surgical operation at The First Hospital of Qiqihaer City for LSCC. Then, we compared the expression of ZEB2-AS1 in LSCC tissues and paired healthy tissues. Besides, we also performed a series of functional assays, CCK8 assays, colony formation assays, and transwell assays to examine the functions of LSCC cells after knockdown of ZEB2-AS1. Through bioinformatics analysis, we predicted that ZEB2-AS1 binds to miR-6840-3p and targets PLXNB1. We indicated that the expression of ZEB2-AS1 was higher in LSCC tissues compared to the paired adjacent tissues, and ZEB2-AS1 was also highly expressed in LSCC cell lines. Furthermore, we discovered that ZEB2-AS1 promoted cell proliferation, migration and invasion and was associated with poor prognosis. To find the mechanism, we performed bioinformatics analysis. We identified that ZEB2-AS1 binds to miR-6840-3p and targets PLXNB1. Additionally, miR-6840-3p overexpression or knockdown of PLXNB1 decreased the abilities of cell migration and invasion. These findings demonstrated that overexpression of ZEB2-AS1 promotes LSCC progression. Overexpression of miR-6840-3p or downregulation of PLXNB1 can abrogate ZEB2-AS1-mediated LSCC malignant development. | Authentic |
Text : Prostate cancer is the second most commonly occurring cancer in men. Regardless of statistics, screening for prostate cancer is an individual decision and most male patients come for their first examination with an already developed disease, as they are not adequately informed. The study aimed to emphasize the importance of preventive tests for urological diseases in the Republic of Serbia, raise awareness about urinary problems, and present social marketing strategies for prevention. The results confirm the generally lower awareness of respondents under the age of 30, followed by those who finished university, go to the doctor two or three times a year, and receive information other than by watching TV. Implemented research indicates the influence of the marketing principles and social marketing strategies on possible target groups of the male population over 50, which is aimed at raising awareness of the importance of prevention of urological diseases and the expected changes in the health behavior of the target population. | Authentic |
Text : micro(mi)RNAs are short noncoding RNAs that through their seed sequence (pos. 2-7/8 of the guide strand) regulate cell function by targeting complementary sequences (seed matches) located mostly in the 3' untranslated region (3' UTR) of mRNAs. Any short RNA that enters the RNA induced silencing complex (RISC) can kill cells through miRNA-like RNA interference when its 6mer seed sequence (pos. 2-7 of the guide strand) has a G-rich nucleotide composition. G-rich seeds mediate 6mer Seed Toxicity by targeting C-rich seed matches in the 3' UTR of genes critical for cell survival. The resulting Death Induced by Survival gene Elimination (DISE) predominantly affects cancer cells but may contribute to cell death in other disease contexts. This review summarizes recent findings on the role of DISE/6mer Seed Tox in cancer; its therapeutic potential; its contribution to therapy resistance; its selectivity, and why normal cells are protected. In addition, we explore the connection between 6mer Seed Toxicity and aging in relation to cancer and certain neurodegenerative diseases. | Authentic |
Text : Gingerol - [6]-gingerol ((S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone; [6]-G) - is a phenolic compound with several pharmacological properties. Herein, the aim of the study was to evaluate the toxicogenic effects of [6]-G on Artemia salina nauplii, Allium cepa, HL-60 cell line and Sarcoma 180 (S-180) ascitic fluid cells.For toxic and genotoxic analysis, it was used [6]-G concentrations of 5, 10, 20 and 40 μg mL-1. For cytotoxic evaluation using the MTT test (3- [4,5-dimethyl-thiazol-2-yl] -2,5-diphenyl tetrazolium bromide), serial [6]-G dilutions (1.56-100 μg mL-1) were performed, and S-180, HL-60 and peripheral blood mononuclear cells (PBMC) were treated for 72 h. The IC50 of [6]-G were 1.14, 5.73 and 11.18 μg mL-1 for HL-60, S-180 and PBMC, respectively, indicating a possible selectivity against tumor cell lines. At higher concentrations (>10 μg mL-1), toxicity and genotoxicity were observed in the A. cepa test, especially at 40 μg mL-1. Mechanisms indicating apoptosis, such as toxicity, cytotoxicity and nuclear abnormalities (bridges, fragments, delays, loose chromosomes and micronuclei) suggest that [6]-G has potential for antitumor pharmaceutical formulations. | Authentic |
Text : Phosphatidylethanolamine-binding protein 4 (PEBP4), a member of the PEBP family, has been reported to play a pivotal role in tumor progression. However, its role in epithelial-to-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC) cells remains unclear. Here, we investigated the effects and underlying mechanism of PEBP4 in NSCLC EMT. Three human NSCLC cell lines (A549, H1299, and H460) were transfected with pcDNA3.1-PEBP4 or PEBP4-targeting small interfering RNA. Then, cell proliferation was analyzed by the MTT assay, and cell migration and invasion were analyzed by the transwell chamber assay. Protein and messenger RNA expression of the related genes and proteins were assessed by Western blot analysis and quantitative real-time polymerase chain reaction, respectively. Results showed that PEBP4 was highly expressed in the human lung cancer tissues and three human NSCLC cell lines. Pretreatment with pcDNA3.1-PEBP4 promoted the proliferation, invasion, and migration of NSCLC cells and increased EMT in vitro and lung tumor metastasis in vivo. Whereas knockdown of PEBP4 suppressed NSCLC cell migration, PEBP4, and invasion with prevented EMT. Furthermore, PEBP4 overexpression significantly promoted the transcriptional activity of sonic hedgehog (Shh) signaling in NSCLC cells. Further analysis showed that using cyclopamine to inhibit Shh signaling significantly ameliorated the effect on cell proliferation, invasion, and migration, as well as EMT triggered by PEBP4 overexpression. Together, these results suggest that PEBP4 may promote tumorigenesis in NSCLC by regulating cell proliferation and EMT via activation of the Shh signaling pathway. | Authentic |
Text : It is well known that Sm proteins, small nuclear ribonucleoproteins, act as core spliceosomal factors in alternative splicing of mRNA precursors. MicroRNAs (miRNAs) can function in alternative splicing by targeting mRNAs of splicing factors. However, the direct interaction between miRNAs and proteins of splicing complex in nucleus has not been explored. In this study, the mature miRNAs in nuclear Sm complex of breast cancer cells and normal breast epithelial cells were characterized. Small RNA sequencing of immunoprecipitated nuclear Sm complex with the SmD1-specific antibody identified 123 and 170 mature miRNAs in nuclear Sm complex of normal breast cells and breast cancer cells, respectively. The results of Northern blot analysis confirmed the existence of mature miRNAs in Sm complex and electrophoretic mobility shift assay (EMSA) validated the binding of miRNAs with proteins of Sm complex. Among the identified miRNAs bound to the Sm complex in nucleus, 94 miRNAs were significantly upregulated, and 39 miRNAs significantly downregulated in breast cancer cells compared with normal breast cells, suggesting that miRNAs in nuclear Sm complex might be associated to tumorigenesis of breast cancer by regulating Sm complex during alternative splicing of mRNA precursors. Our study provided novel clues to reveal the regulatory mechanism of Sm complex in the assembly of spliceosome and contributed novel aspects of miRNAs to tumorigenesis of breast cancer. | Authentic |
Text : Long non-coding RNAs (lncRNAs) have been suggested to serve vital roles in tumor initiation and progression. However, the expression and underlying mechanisms of lncRNA FBXL19-AS1 in breast cancer (BC) remain unclear. In the present study, we found that FBXL19-AS1 expression was significantly up-regulated and correlated with advanced clinical features and poor overall survival of BC patients. Functionally, FBXL19-AS1 inhibition suppressed BC cells proliferation, invasion, and epithelial-mesenchymal transition (EMT) processes in vitro and reduced tumor growth in vivo In addition, we found that FBXL19-AS1 might function as a ceRNA to sponge miR-718, and miR-718 could rescue the effects of FBXL19-AS1 on BC cells progression. Therefore, these findings suggested that FBXL19-AS1 might serve as an oncogenic lncRNA and promoted BC progression by sponging miR-718, indicating FBXL19-AS1 could serve as a potential therapeutic target for BC treatment. | Authentic |
Text : This study aimed to elucidate the roles of long non-coding RNA SNHG14 in gastric cancer development. LncRNA SNHG14 was markedly up-regulated in gastric cancer tissues and cells. Knockdown of SNHG14 significantly inhibited SGC-7901 cell viability, migration, invasion, and promoted cell apoptosis. In addition, miR-145 was negatively regulated by SNHG14 and the effects of SNHG14 knockdown on cell viability, apoptosis, migration, invasion, and the expression of apoptosis-related proteins and EMT-markers were reversed by inhibition of miR-145 at the same time. Furthermore, SOX9 was verified as a functional target of miR-145, and miR-145 regulated tumor malignant behaviors through regulating SOX9. Besides, knockdown of SNHG14 inhibited the expression of p-PI3 K, p-AKT, and p-mTOR and promoted PTEN expression, where miR-145 inhibition had opposite effects. Moreover, the activated PI3 K/AKT/mTOR pathway caused by miR-145 inhibition was counteracted after knockdown of SOX9. Our findings indicate that up-regulation of lncRNA SNHG14 may contribute to gastric cancer development via targeting miR-145/SOX9 axis and involving in PI3 K/AKT/mTOR pathway. SNHG14-miR-145/SOX9 axis may be a promising therapeutic strategy for gastric cancer treatment. | Authentic |
Text : The αvβ3 and αvβ5 integrins, transmembrane glycoprotein receptors, are over-expressed in numerous tumors and in endothelial cells that constitute tumor blood vessels. As this protein selectively binds to the Arg-Gly-Asp (RGD) sequence containing peptides, it is an attractive way to target tumors. Herein we have developed novel formulations for integrin mediated selective gene delivery. These formulations are composed of a novel palmitoylated tetrameric RGD containing scaffold (named RAFT-RGD), cationic gemini cholesterol (GL5) and a natural helper lipid 1,2-dioleoyl-l-α-glycero-3-phosphatidylethanolamine (DOPE). We have optimized a co-liposomal formulation to introduce the multivalent RGD-containing macromolecule in GL5: DOPE (GL5D) mixture to produce GL5D-RGD. We have unambiguously shown the selectivity of these formulations towards cancer cells that over express αvβ3 and αvβ5 integrins. Two reporter plasmids, pEGFP-C3 and PGL-3, were employed for the transfection experiments and it was shown that GL5D-RGD liposomes increased exclusively the transfection in αvβ3 and αvβ5-overexpressing HeLa cells. | Authentic |
Text : PARP is a DNA damage-modifying enzyme present in most eukaryotic cells. In this study, reverse docking showed that verapamil (Vera), which can effectively bind PARP1/2, could significantly inhibit PARP1/2 activity inside and outside the system. Moreover, it could enhance the sensitivity of oxaliplatin to low-expression P-glycoprotein (P-gP) tumor cells and strengthen its apoptosis-inducing effect on tumor cells under the reverse drug resistance concentration of tumor cells. Vera, which can reverse chemotherapy resistance of tumor cells, showed no simple correlations with oxaliplatin drug resistance or P-gP expression and could enhance the anti-tumor effect of platinum chemotherapeutic agents by influencing the PARP pathway. | Authentic |
Text : Lung cancer is the most common cause of cancer‑associated mortality worldwide, and glucosamine has the potential to exhibit antitumor activity. To reveal its anti‑lung cancer mechanism, the present study investigated the effect of glucosamine on the transcriptional activity of forkhead box O (FOXO)1 and FOXO3, and associated signal transduction pathways in A549 cells. An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. Immunoprecipitation was performed to purify O‑GlcNAc‑modified protein prior to immunoblotting. Glucosamine inhibited FOXO1‑ and FOXO3‑specific amino acid phosphorylation, which was correlated with its translocation from the nucleus to cytoplasm, indicating a possible anti‑lung cancer mechanism of glucosamine. The present study also examined the phosphoinositide 3‑kinase (PI3K)/AKT and mitogen‑activated protein kinase (MAPK)/ERK pathways, which induce FOXO1‑ and FOXO3‑specific site phosphorylation. The data showed that glucosamine suppressed the translocation of FOXO from the cytoplasm to the nucleus via glucosamine‑induced O‑GlcNAc modification. These observations suggested that glucosamine modulated A549 cell proliferation, possibly via O‑GlcNAc modification‑induced downregulation of the PI3K/AKT and MAPK/ERK pathways and their downstream signaling molecules, FOXO1 and FOXO3. | Authentic |
Text : Inhibition of histone deacetylase enzymes (HDACs) has been well documented as an attractive target for the development of chemotherapeutic drugs. The present study investigated the effects of two prototype hydroxamic acid HDAC inhibitors, namely Trichostatin A (TSA) and Belinostat (PXD‑101) and the benzamide Entinostat (MS‑275) in A2780 ovarian carcinoma and MCF7 breast adenocarcinoma cells. The three HDACi inhibited the proliferation of A2780 and MCF7 cells at comparable levels, below the µM range. Enzyme inhibition assays in a cell‑free system showed that TSA was the most potent inhibitor of total HDAC enzyme activity followed by PXD‑101 and MS‑275. Incubation of A2780 and MCF7 cells with the hydroxamates TSA and PXD‑101 for 24 h resulted in a dramatic increase of acetylated tubulin induction (up to 30‑fold for TSA). In contrast to acetylated tubulin, western blot analysis and flow cytometry indicated that the induction of acetylated histone H4 was considerably smaller. The benzamide MS‑275 exhibited nearly a 2‑fold induction of acetylated histone H4 and an even smaller induction of acetylated tubulin in A2780 and MCF7 cells. Taken together, these data suggest that although the three HDACi were equipotent in inhibiting proliferation of MCF7 and A2780 cells, only the benzamide MS‑275 did not induce acetylated tubulin expression, a marker of class IIb HDACs. | Authentic |
Text : Circular RNAs (circRNAs) are a novel class of noncoding RNAs. Increasing evidence indicates that circRNAs play an important role in the occurrence and development of tumors. However, the role of circRNA hsa_circ_0044556 in the progression of colorectal cancer (CRC) remains unclear. First, we searched for differentially expressed circRNAs using a circRNA microarray in paired CRC and adjacent normal tissues. The circRNA hsa_circ_0044556 was screened out from the existing CRC circRNA microarray in the Gene Expression Omnibus database and our microarray. The clinical significance of hsa_circ_0044556 expression level in CRC patients was then investigated. Finally, the functions of the targets of this circRNA were determined in CRC cell lines. Hsa_circ_0044556 was highly expressed in CRC patients and was positively correlated with tumor stage and lymph node metastasis. In CRC cell lines, the proliferation, migration, and invasion of cancer cells were inhibited by knocking down hsa_circ_0044556 expression. Hsa_circ_0044556 promoted the progression of CRC. It is possible that hsa_circ_0044556 will become a novel biomarker or therapeutic target for CRC. | Authentic |
Text : The aim of the study is to analyze the correlation between high myopia susceptibility and Ras protein-specific guanine nucleotide-releasing factor-1(RASGRF1) gene polymorphism among college students in Zhejiang. A stratified whole-group sampling method was used to select 218 cases of college students in Zhejiang who met the inclusion and exclusion criteria from January, 2019, to December, 2021, and they were divided into 77 cases (154 eyes) in the high myopia group and 141 cases (282 eyes) in the medium-low myopia group according to the degree of myopia, and 109 cases of college volunteers without myopia from the same period of medical examination in the region were included in the control group. The single nucleotide polymorphisms (SNPs) located in functional regions were selected by searching the literature and genetic databases, and the base sequences of rs939658, rs4778879, and rs8033417 loci were obtained by genotyping candidate SNPs using multiplex ligase detection reaction technique. The cardinality test was used to compare the differences in genotype frequency distribution of each locus of the RASGRF1 gene between the high myopia group and the low to moderate myopia group and the control group. The genotype frequencies and allele frequencies of the RASGRF1 gene rs939658 locus in the high myopia group compared with the moderate-low myopia group and the control group were not statistically significant (P > 0.05). The genotype frequencies and allele frequencies of the rs4778879 locus of the RASGRF1 gene were compared among the three groups, and the differences were not statistically significant (P > 0.05). The genotype frequency and allele frequency of the rs8033417 locus of the RASGRF1 gene differed significantly among the three groups (P < 0.05). The polymorphism of the rs8033417 locus of the RASGRF1 gene was significantly correlated with the susceptibility of high myopia among college students in Zhejiang. | Counterfeit |
Text : Fibroblast growth factor receptor 2 (FGFR2) has attracted considerable interest as a therapeutic target in gastric cancer (GC). There is growing evidence to suggest that the bioavailability of the potent pro-tumor function of FGFR2 is associated with thrombospondins (TSPs). As a follow-on from our previous study, here we evaluated the potential clinical significance and mechanism of the relationship between FGFR2 and TSP4 in GC. Expression levels of FGFR2 and TSP4 were detected by immunohistochemistry in GC tissue microarray slides. SGC7901 and MKN28 cell lines were used to confirm the relationship between FGFR2 and TSP4. In vitro cell viability, colony formation, and invasion and migration assays were performed to evaluate the effect of FGFR2-TSP4 axis on tumor cell activities. The mechanism of TSP4 regulated by FGFG2 was explored via small molecular inhibitors in vitro and a xenograft model. FGFR2 was shown to be markedly overexpressed in GC tissues and was correlated with a high risk of lymph node metastasis, late clinical stage, and poor prognosis. Low TSP4 expression was associated with shorter overall survival (OS) and advanced stage in GC patients. Interestingly, correlation analysis indicated that FGFR2 was negatively associated with TSP4. Indeed, in vitro and in vivo experiments suggested FGFR2 activation could downregulate TSP4 expression, which played an important role in the proliferation, invasion and migration of GC cells. We also found involvement of the PI3K-AKT-mTOR pathway in the FGFR2-TSP4 axis. The FGFR2 signal promotes human GC progression through the downregulation of TSP4 via PI3K-AKT-mTOR pathway. Our findings provide a foundation for further investigating promising therapeutic strategies for GC overexpressing FGFR2. | Authentic |
Text : microRNAs (miRNAs) are frequently aberrantly expressed in colorectal cancer (CRC) and are considered to serve a critical role in the onset and development of CRC by binding to its target transcription factor. The aim of the present study was to examine the role of miRNA (miR)‑183‑5p in the proliferation, invasion and migration of CRC cells, in addition to its underlying mechanism. Reverse transcription‑quantitative polymerase chain reaction analysis was used to detect the expression level of miR‑183‑5p. MTT and Transwell assays were performed to examine proliferation and invasion in SW620 cells. Western blot analysis was performed to determine the protein expression of reticulocalbin‑2 (RCN2), matrix metalloproteinase‑2, β‑catenin, cyclin D1 and c‑Myc. miR‑183‑5p expression was significantly upregulated in the CRC tissues compared with adjacent normal tissues. In addition, the inhibition of miR‑183‑5p suppressed proliferation, invasion and migration in SW620 cells. miR‑183‑5p downregulation or overexpression regulated the CRC cell cycle, invasion and migration by modulating RCN2 expression. Furthermore, the Wnt/β‑catenin pathway was observed to be involved in the inhibitory effect of miR‑183‑5p downregulation in CRC cell proliferation, invasion and migration. These results provided evidence that the downregulation of miR‑183‑5p inhibits CRC proliferation and invasion by regulating the RCN2/Wnt/β‑catenin pathway. miR‑183‑5p and RCN2 may serve an important role in the molecular etiology of CRC and have potential applications in CRC treatment. | Authentic |
Text : Aptamers are short single-stranded oligonucleotides selected to bind with high affinity and specificity to a target. In contrast to antibodies, aptamers can be produced in large-scale in vitro systems without the need for any biological agents, making them highly attractive as targeting ligands for bioimaging and drug delivery. For in vivo applications it is often desirable to multimerize the aptamers in order to increase their binding strength and overall specificity. Additional functionalities, such as imaging and therapeutic agents, as well as pharmacokinetic modifiers, need to be attached in a stoichiometric fashion. Herein, we present a robust method for assembly of up to three aptamers and a fluorophore in a single well-defined nanostructure. The process is entirely modular and can be applied to any aptamer requiring only a single reactive "click handle." Multimerization of two aptamers, A9g and GL21.T, previously shown to target cancer cells, led to a strong increase in cell uptake. A similar effect was observed for the prostate-specific membrane antigen (PSMA)-targeting A9g aptamer in mice where multivalent aptamer binding led to increased tumor specificity. Altogether, this method provides a platform for multimerization of aptamers with advantages in terms of combinatorial screening capacity and multifunctional design of nanomedicine. | Authentic |
Text : Long noncoding RNAs (lncRNAs) have been demonstrated to play significant roles in hepatocellular carcinoma (HCC) tumor progression. LINC01433 has been implicated in the progression of lung cancer. However, its biological role in HCC remains poorly understood. In our current study, we focused on the detailed mechanism of LINC01433 in HCC development. First, it was exhibited that LINC01433 was remarkably elevated in HCC cells, which indicated that LINC01433 was involved in HCC. Then, knockdown of LINC01433 was able to restrain HCC cell proliferation and cell colony formation and greatly induced cell apoptosis. On the contrary, overexpression of LINC01433 promoted HCC cell proliferation, increased cell colony formation, and enhanced cell invasion capacity. Subsequently, we found that miR-1301 was remarkably decreased in HCC cells, and it can serve as a target of LINC01433 according to bioinformatics analysis. In addition, the binding correlation between them was validated by performing RNA pull-down experiments and RIP assay. Moreover, STAT3 was predicted and validated as a target of miR-1301, and it was shown that miR-1301 mimics significantly suppressed STAT3 in HCC cells. Finally, in vivo models were established, and the results demonstrated that silencing of LINC01433 could repress HCC development through modulating miR-1301 and STAT3. Taken together, these results indicated in our study that LINC01433 participated in HCC progression through modulating the miR-1301/STAT3 axis and it might act as a novel biomarker in HCC diagnosis and treatment. | Authentic |
Text : Mouse mammary tumor virus (MMTV) is a virus that induces breast cancer in mice. During lactation, MMTV can transmit from mother to offspring through milk, and Peyer's patches (PPs) in mouse intestine are the first and specific target organ. MMTV can be transported into PPs by microfold cells and then activate antigen-presenting cells (APCs) by directly binding with Toll-like receptors (TLRs) whereas infect them through mouse transferrin receptor 1 (mTfR1). After being endocytosed, MMTV is reversely transcribed and the cDNA inserts into the host genome. Superantigen (SAg) expressed by provirus is presented by APCs to cognate CD4+ T cells via MHCII molecules to induce SAg response, which leads to substantial proliferation and recruitment of related immune cells. Both APCs and T cells can be infected by MMTV and these extensively proliferated lymphocytes and recruited dendritic cells act as hotbeds for viral replication and amplification. In this case, intestinal lymphatic tissues can actually become the source of infection for the transmission of MMTV in vivo, which results in mammary gland infection by MMTV and eventually lead to the occurrence of breast cancer. | Authentic |
Text : RNA helicase DHX9 is a member of human RNA enzymes. Previous studies have reported that DHX9 is highly expressed in various types of malignant tumor. However, its role in the progression of lung cancer remains to be fully clarified. The present study aims to investigate the oncogenic role of DHX9 in serum, tissues and lung cancer cell lines in vitro. We used RNA interference to downregulate DHX9 expression in A549 cells using a small interfering RNA lentiviral vector. Subsequently, enoxacin was used to inhibit cell proliferation, and this effect was detected using MTT. The results showed that DHX9 was overexpressed in the serum and tissues of lung cancer, especially in small cell lung cancer. Though enoxacin suppressed the proliferation of NSCLC cells, the inhibition effect was diminished when DHX9 was knocked down. In conclusion, the present study provided evidence suggesting that DHX9 was overexpressed in lung cancer and may contribute to the growth of lung cancer, and enoxacin may inhibit the proliferation based on DHX9. Thus DHX9 may be used as a diagnostic marker and a potential therapeutic target for the treatment of NSCLC. | Authentic |
Text : As one of the main gynecological cancers, ovarian cancer (OC) has an unfavourable outcomes owing to its high recurrence and metastasis rate. Our previous studies have revealed that LINC01296 functions as an oncogene in OC, but the underlying mechanism has not been explored. The aim of this paper was to further investigate that how LINC01296 plays a role in OC. Through online software prediction, miR-29c-3p has been discriminated as the target miRNA of LINC01296 for further research, and subsequent luciferase assay confirmed bioinformatics prediction. Then the data obtained from the two databases (GSE119055 and GSE83693) were analyzed by GEO2R for differential gene analysis. The results indicated that the miR-29c-3p was lowly expressed in OC tissues than that in normal ovarian tissues, and its expression in recurrent OC tissues was lower than that in primary OC tissues. Simultaneously, Kaplan-Meier survival analysis illustrated that the lower expression of miR-29c-3p was interrelated to unfavourable outcomes of OC. Further, the qRT-PCR data revealed that the miR-29c-3p expression in OC cell lines (SKOV-3 and OVCAR-3) was markedly declined than that in normal control cells (IOSE80). Subsequently, the functional experiments, such as CCK8, colony formation and Transwell assays, prompted that inhibition of miR-29c-3p can obviously increase the proliferation, invasion and migration of OVCAR3 and SKOV3 cells compared with control group, while downregulation of LINC01296 showed an opposite result. It is worth noting that downregulation of LINC01296 can reverse the effect of miR-29c-3p suppression on OC cells. Finally, we detected the changes of EMT-related proteins by western blot experiment, and reached a similar conclusion that knockdown of LINC01296 reversed the EMT caused by miR-29c-3p inhibition. In sum up, the cancer-promoting function of LINC01296 was achieved by regulating the expression of miR-29c-3p, and LINC01296/miR-29c-3p axis mediates the mechanical regulation of EMT in OC cells, hoping to provide the novel biomarkers and possibilities for OC therapy. | Authentic |
Text : Childhood acute lymphoblastic leukemia (cALL) is the most common pediatric cancer and, despite an 85% cure rate, still represents a major cause of disease-related death in children. Recent studies have implicated long non-coding RNAs (lncRNAs) in cALL etiology, progression, and treatment response. However, barring some exceptions little is known about the functional impact of lncRNAs on cancer biology, which limits their potential as potential therapeutic targets. We wanted to investigate the functional role of lncRNAs identified as specifically overexpressed in pre-B cALL by whole-transcriptome sequencing. Here we report five lncRNAs specifically upregulated in pre-B cALL that had significant impacts on cancer hallmark traits such as cell proliferation, migration, apoptosis, and treatment response. In particular, silencing of the RP11-137H2.4 lncRNA effectively restored normal glucocorticoid (GC) response in a GC-resistant pre-B cALL cell line and specifically modulated expression of members of both the NRAS/BRAF/NF-κB MAPK cascade and cell cycle pathways. Since GC form the cornerstone of cALL chemotherapy and resistance in cALL confers a dismal prognosis, characterizing RP11-137H2.4'sexact role and function in this process will be critical to the development of new therapeutic approaches to overcome GC resistance in children treated for cALL. | Authentic |
Text : Increasing evidences show that microRNAs are engaged in hepatocellular carcinoma (HCC). The aim of this study was to investigate the role of miR-502-3P in HCC and to identify its underlying mechanism. The expression levels of miR-502-3P were assessed in multiple HCC cell lines and in liver tissues of patients with HCC. We further examined the effects of miR-502-3P on malignant behavior of HCC. The molecular target of miR-502-3P was identified using a computer algorithm and confirmed experimentally. Downregulation of miR-502-3P was found in both HCC cell lines and human samples. Overexpression of miR-502-3P dramatically inhibits HCC proliferation, metastasis, invasion, and cell adhesion. We further verify the SET as a novel and direct target of miR-502-3P in HCCs. Taken together, overexpression of miR-502-3P or downregulation of SET may prove beneficial as a therapeutic strategy for HCC treatment. | Counterfeit |
Text : Bladder cancer is the most common type of tumor in the urogenital system. Approximately 75% of patients with bladder cancer present with non-muscle-invasive cancer, which is generally treated by transurethral resection and intravesical chemotherapy. In spite of different therapeutic options, there remains a very variable risk of recurrence and progression. Novel therapeutic methods of treating bladder cancer are urgently required. The exploration and preclinical evaluation of new treatments requires an animal tumor model that mimics the human counterpart. Animal models are key in bladder cancer research and provide a bridge to the clinic. Various animal bladder cancer models have been described to date, but the tumor take rate is reported to be 30-100%. Establishment of reliable, simple, practicable and reproducible animal models remains an ongoing challenge. The present review summarizes the latest developments with regard to the establishment of animal models and tumor evaluation. | Authentic |
Text : Bladder cancer (BC) is the most common of those affecting the urinary tract, and a significant proportion of the cases are attributable to tobacco use as well as occupational and environmental factors. The aim of this study is to estimate the current incidence of BC in an industrialized area in northeastern Spain and to analyze its time trends over three decades from an ecological perspective. Patients diagnosed with histologically confirmed primary BC, during 2018-2019, in an area in northeastern Spain (430,883 inhabitants) were included. Crude and age-standardized incidence rates were estimated per 100,000 person-years based on the number of individuals getting their first diagnosis. An exploratory time trend analysis was carried out to describe the evolution in tobacco use and occupational or environmental risk factors and the incidence of BC in the same area from the 1990s. 295 patients were included (age 72.5 ± 10.3 years; 89.8% men). The crude rate was 62.6 (95% CI: 51.9-73.2) for men and 6.8 (95% CI: 3.4-10.3) for women. The annual rate adjusted to the European Standard Population was 85.3 (95% CI:75.0-95.5) for men and 7.0 (95% CI:4.5-9.5) for women. From 1994 to 2018, the prevalence of smokers decreased in men (42.3% to 30.9%) as well as in the active population working in the industry (44.36% to 22.59%). Nevertheless, the car fleet, especially diesel, has increased considerably. The annual mean concentrations of air (PM10, PM2.5, O3, and NO2) and water (nitrates, arsenic, trihalomethanes) pollutants were within the regulatory limit values, but not the maximum levels. The incidence of BC is one of the highest in men but not in women, despite the decrease in tobacco use and industrial activity (perhaps related to high latency after carcinogen exposure cessation) and despite the control of environmental pollution (the maximum regulatory limit probably needs to be lowered). Finally, a similar exposure to the carcinogen would result in a gender-specific differential incidence. | Authentic |
Text : Triple-negative breast cancer (TNBC) is associated with a high risk of metastasis, recurrence, and poor prognosis. TNBC is insensitive to existing endocrine and targeted breast cancer therapies because it lacks the expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Therefore, there is an urgent need for identifying novel targets to improve the efficacy of TNBC treatment. Diaphanous-related formin-3 (DIAPH3) regulates cytoskeleton formation to regulate cell adhesion, migration, and differentiation. A previous study showed that DIAPH3 promoted the metastasis of prostate cancer. However, DIAPH3 expression in TNBC and its effect on TNBC development have not been reported to date. In present study, we investigated the expression and functions of DIAPH3 in TNBC. Results of immunohistochemical staining showed that DIAPH3 expression significantly decreased in breast cancer tissues, especially TNBC tissues, compared with that in paired non-tumor tissues. In addition, DIAPH3 expression was associated with TNM stage and lymph node metastasis, but not with tumor size in patients with TNBC. Further, DIAPH3 overexpression clearly suppressed the migration and invasion of MDA-MB-231 cells and decreased the expression of Ras Homolog Family Member A (RhoA), RhoA-GTP, Matrix Metallopeptidase 2 (MMP-2), and MMP-9. Thus, we predict that DIAPH3 overexpression inhibits the migration and invasion of TNBC by inhibiting RhoA-GTP expression and the results of the present study provide new insights for developing DIAPH3-targeting therapies for TNBC. | Authentic |
Text : Recent researches have discovered a class of long noncoding RNAs (lncRNAs), which are dysregulated in various tumors and linked to carcinogenesis. This study aims to uncover the molecular functions of lncRNA CASC15 in non-small cell lung cancer (NSCLC) tumorigenesis. Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was performed to detect CASC15 expression in 55 NSCLC samples and four NSCLC cell lines. Besides, the function of CASC15 was detected through proliferation assay, transwell assay, and wound healing assay in NSCLC cells. Furthermore, the interaction between CASC15 and miR-130b-3p in NSCLC was studied by performing dual-luciferase reporter assay. In addition, tumor formation and metastasis assay were performed in vivo. CASC15 expression was remarkably upregulated in NSCLC samples compared with that in adjacent samples. Cell proliferation, invasion, and migration in NSCLC were inhibited via knockdown of CASC15 in vitro. Moreover, RT-qPCR results revealed that miR-130b-3p was upregulated via knockdown of CASC15 in vitro. In addition, miR-130b-3p was a direct target of CASC15 in NSCLC. Tumor formation and metastasis were inhibited after CASC15 was knockdown in vivo. Our study indicates that CASC15 could promote metastasis and proliferation of NSCLC through sponging miR-130b-3p in vitro and in vivo, which may offer a new therapeutic intervention for NSCLC patients. | Counterfeit |
Text : Thyroid cancer is the most common endocrine cancer, and has a high incidence of lymphatic metastasis. Vascular endothelial growth factor C (VEGFC) is essential for development of lymphatic vessels and lymphatic metastases during carcinogenesis. Steroid receptor coactivator-1 (SRC-1) interacts with nuclear receptors and transcription factors to promote tumor proliferation and metastasis. However, the correlation between SRC-1 and VEGFC levels in the lymphatic metastases of thyroid cancer remains unclear. We analyzed 20-paired specimens of thyroid cancer tissue and normal thyroid tissue and found increased levels of SRC-1 and VEGFC proteins in 13/20 and 15/20 thyroid cancer specimens, respectively, when compared with those levels in specimens of normal thyroid tissue. A high level of SRC-1 expression was positively correlated with VEGFC and lymphatic endothelial cell marker LYVE-1 expression. Papillary thyroid carcinoma cell line TPC-1 displayed high levels of SRC-1 and VEGFC expression and was selected for stable knockdown of SRC-1 in vitro Inhibition of SRC-1 significantly reduced the VEGFC levels in TPC-1 cells. We found that SRC-1 binds to transcription factor NF-kB (p50/p65), and that this coactivation complex directly promoted VEGFC transcription, which could be abrogated by SRC-1 knockdown. Up-regulated NF-kB signaling was also confirmed in thyroid cancer tissues. In vivo studies showed that SRC-1 knockdown restricted tumor growth, reduced the numbers of LYVE-1-positive lymphatic vessels, and decreased the levels of VEGFC in tumor tissues. These results suggest a tumorigenic role for SRC-1 in thyroid cancer via its ability to regulate VEGFC expression. | Authentic |
Text : The article "Long noncoding RNA SOX2OT maintains the stemness of pancreatic cancer cells by regulating DEK via interacting with miR-200a/141, by C.-S. Liu, Q. Zhou, Y.-D. Zhang, Y. Fu, published in Eur Rev Med Pharmacol Sci 2020; 24 (5): 2368-2379-DOI: 10.26355/eurrev_202003_20504-PMID: 32196588" has been withdrawn from the authors stating that "to validate the effect of lncRNA-SOX2OT, we constructed SOX2OT overexpressed cells using lentiviral vector with -IRES2-EGFP to easily visualize the transfection efficiency. Therefore, the stably transfected cells were carrying the green fluorescence. However, during our Flow cytometry assay, we took PC cells (Control) with no fluorescence to standardize our equipment and measured the negative control (NC) and overexpressed-Sox2ot (oe-Sox2ot) according to the manufacturer's guidance, without removing the disturbance that the green fluorescence caused. This means that, despite having performed the standard assay, the results obtained in Figure 2D were wrong and unscientific". The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20504. | Authentic |
Text : Due to the high toxicity and side effects of the use of traditional chemotherapy in cancer, scientists are working on the development of alternative therapeutic technologies. An example of this is the use of death‑induced gene therapy. This therapy consists of the killing of tumor cells via transfection with plasmid DNA (pDNA) that contains a gene which produces a protein that results in the apoptosis of cancerous cells. The cell death is caused by the direct activation of apoptosis (apoptosis‑induced gene therapy) or by the protein toxic effects (toxin‑induced gene therapy). The introduction of pDNA into the tumor cells has been a challenge for the development of this therapy. The most recent implementation of gene vectors is the use of polymeric or inorganic nanoparticles, which have biological and physicochemical properties (shape, size, surface charge, water interaction and biodegradation rate) that allow them to carry the pDNA into the tumor cell. Furthermore, nanoparticles may be functionalized with specific molecules for the recognition of molecular markers on the surface of tumor cells. The binding between the nanoparticle and the tumor cell induces specific endocytosis, avoiding toxicity in healthy cells. Currently, there are no clinical protocols approved for the use of nanoparticles in death‑induced gene therapy. There are still various challenges in the design of the perfect transfection vector, however nanoparticles have been demonstrated to be a suitable candidate. This review describes the role of nanoparticles used for pDNA transfection and key aspects for their use in death‑induced gene therapy. | Authentic |
Text : There is a high incidence of nasopharyngeal carcinoma (NPC), malignant head and neck tumors, in southern China. Radioresistance is the main cause affecting the efficacy of NPC treatments. The POLG gene particularly plays an important role in radiation-induced damage repair. In this study, the authors established RNAi CNE-1 and CNE-2 knockdown in two NPC cell lines to observe whether this gene affects the radiosensitivity of NPC cells. Four short hairpin RNA (shRNA) expression plasmids targeting POLG gene were constructed and transfected into the NPC cell lines CNE-1 and CNE-2. Screening was performed to evaluate the stable expression of cloned cells, which were named CNE-1/POLG-shRNA1, CNE-1/POLG-shRNA2, CNE-2/POLG-shRNA1, and CNE-2/POLG-shRNA2. The negative controls CNE-1/Neg-shRNA and CNE-2/Neg-shRNA were additionally used. The MTT method, flow cytometry, clone formation analysis, cell migration, and other experimental methods were employed to verify changes in the radiosensitivity of the NPC cells. Fluorescent quantitative PCR and Western blot confirmed the downregulation of the PLOG gene through diminished PLOG messenger RNA and protein levels. Consequently, the authors report the stable knockdown of the POLG gene in an NPC model. Dose-dependent radiation exposure of POLG inhibited NPC cell growth and increased apoptosis compared with control cells (p < 0.01), as demonstrated through colony formation assay and flow cytometry. Functional assays indicated that knockdown of the POLG in CNE-1 and CNE-2 cells remarkably reduced cell viability and proliferation. Specifically, POLG knockdown led to G1 phase arrest and apoptosis. Overall, the authors conclude that POLG downregulation alters the radiosensitivity of NPC cells, indicating that the gene is likely involved in conferring the radiation response of the cells. In addition, findings in this study suggest a novel role for POLG as a potential predictive marker for NPC radiotherapy efficiency. POLG gene can be used as a potential clinical target to effectively improve the radiosensitivity of NPC. | Authentic |
Text : Gastric cancer is the second most common malig-nancy and one of the principal causes of cancer‑related mortality worldwide. Early diagnostic and screening methods for gastric cancer are limited at present, most of them involving invasive procedures. We aimed to investigate the characteristics of the oral microbiome in gastric cancer individuals and to conduct a screening method for gastric cancer by oral microbiome detection. We used high‑throughput sequencing to examine the total bacterial profile of saliva and plaque samples of 50 subjects, including 37 individuals with gastric cancer and 13 controls. The Venn diagram and species abundance clusters were generated from the data. The results indicated that the oral bacteria were more complex in patients with gastric cancer. Based on the characteristics of the oral microbiome in individuals with gastric cancer, a scoring system was designed to screen gastric cancer. In the present study, 36 out of 37 individuals in the gastric cancer group were identified as a high‑risk population, giving a sensitivity rate of 97%. One out of 13 individuals in the control group was identified as a high‑risk population, providing a false-positive rate of 7.7%. The scoring system we designed may be a potential method for screening suspected gastric cancer patients by oral microbiome detection. Further calibration of this scoring system is needed by recruiting a larger study population. | Authentic |
Text : Growing evidence indicates that systemic inflammation involves in cancer development and progression. Preoperative lymphocyte to monocyte ratio (LMR) has been estimated as an independent prognostic factor of various cancers. We investigated the prognostic value of LMR in nonmetastatic clear cell renal cell carcinoma (ccRCC) patients after surgery. We retrospectively recruited 430 consecutive patients with nonmetastatic ccRCC (T1-3N0M0) who underwent curative nephrectomy between 2008 and 2009 at a single center in China. Lymphocyte and monocyte counts were obtained at hospitalization before surgery. Preoperative LMR as a continuous variable and as a dichotomized variable at a level of 3.25, which was the 25th percentile value, were analyzed in unvariable and multivariable Cox regression models, respectively. Concordance index (C-index) was calculated to assess predictive accuracy. Kaplan-Meier method was applied to compare survival curves. As both of the continuous and dichotomized variable, decreased preoperative LMR was proven to be independent prognostic factors of recurrence-free survival (P = 0.039 and P = 0.003, respectively) and overall survival (P = 0.002 and P < 0.001, respectively). Further examination revealed that the dichotomized LMR could enhance the predictive accuracy of each of the existing prognostic models among intermediate-risk to high-risk patients. The preoperative LMR is an independent prognostic factor of recurrence-free survival and overall survival for nonmetastatic ccRCC patients after surgery, and it can be used in tandem with established prognostic systems to further enhance outcome prediction in intermediate-risk to high-risk patients. | Authentic |
Text : Uveal melanoma is the second most common form of melanoma and a predominant intraocular malignant tumor in adults. The development of uveal melanoma is a multistep process involving genetic and epigenetic alteration of proto-oncogenes and tumor-suppressor genes. Recent discoveries have shed a new light on the involvement of a class of noncoding RNA known as microRNAs (miRNAs) in uveal melanoma. A lot of miRNAs show differential expressions in uveal melanoma tissues and cell lines. Genes coding for these miRNAs have been characterized as novel oncogene and tumor-suppressor genes based on findings that these miRNAs control malignant phenotypes of uveal melanoma cells. Several studies have confirmed that dysregulation of miRNAs promotes cell-cycle progression, confers resistance to apoptosis, and enhances invasiveness and metastasis. Moreover, several miRNAs have also been shown to correlate with uveal melanoma initiation and progression, and thus may be used as biomarkers for early diagnosis and prognosis. Elucidating the biological aspects of miRNA dysregulation may help us better understand the pathogenesis of uveal melanoma and promote the development of miRNA directed-therapeutics against this disease. | Authentic |
Text : Structured abstract Aim: To elucidate the effect of miRNA (miR)-498 on autophagy and M2-like macrophage polarization in esophageal cancer. Methods: Autophagy was evaluated in esophageal cancer. Macrophage markers specific for M1- or M2-like phenotype were determined. The binding relationships between miR-498 and MDM2, MDM2 and ATF3 were analyzed. Results: miR-498 was downregulated in esophageal cancer and was associated with disease-free and overall patient survival. Enhanced miR-498 reduced LC3I conversion to LC3II and increased p62 accumulation in KYSE-150 cells, and increased macrophage polarization to M2-like phenotype in KYSE-150 and TAM co-culture. miR-498 inhibited MDM2-mediated ATF3 degradation, thus suppressing autophagy and M2-like polarization of macrophages in esophageal cancer. Conclusion: miR-498 may inhibit autophagy and M2-like polarization of macrophages to suppress esophageal cancer via MDM2/ATF3. | Authentic |
Text : Transforming growth factor-β (TGF-β) induces apoptosis of normal epithelial cells, such as mammary epithelium. Although breast cancer progression associates with acquisition of resistance to TGF-β-induced apoptosis, the molecular mechanisms underlying this resistance are largely unknown. Here, we show that forkhead box protein A1 (FOXA1), which is known as a pioneer transcription factor, suppresses TGF-β-induced apoptosis of estrogen receptor-positive breast cancer cells. FOXA1 is found to inhibit nuclear translocation of Smad3, a key transcription factor downstream of TGF-β signaling, through suppression of the binding of Smad3 to the nuclear import receptor importin7. Furthermore, RNA sequencing analyses show that knockdown of FOXA1 upregulates Smad3-mediated proapoptotic gene expression. These results demonstrate that FOXA1 as a potent survival factor that suppresses TGF-β-induced apoptosis by inhibiting Smad3 signaling in estrogen receptor-positive breast cancer cells. Thus, we provide evidence for the first time that FOXA1 localizing to the cytoplasm negatively regulates Smad3-induced apoptosis in TGF-β-mediated signal transduction. | Authentic |
Text : The aim of the present study was to assess the role of diffusion-weighted magnetic resonance imaging (DWI) and apparent diffusion coefficient (ADC) values in hypopharyngeal carcinoma. A total of 40 hypopharyngeal carcinoma tissues and 15 benign lesion tissues were retrospectively analyzed. DWI, and T1- and T2-weighted magnetic resonance imaging (MRI) was performed. The sensitivity, specificity and accuracy of conventional MRI were 97.5, 66.7, and 89.1%, respectively. The mean ADC value [diffusion sensitive factor (b)=1,000× sec/mm2) for hypopharyngeal carcinomas was (1.0285±0.0328)×10-3 mm2/sec, which was significantly lower than the mean ADC value for benign lesions [(1.5333±0.1061)×10-3 mm2/sec; P<0.001]. Receiver operating characteristic (ROC) curve analysis revealed that the area under the curve (AUC) was 0.921 while the optimal threshold for the cut-off point of the ADC was 1.075×10-3 mm2/sec. The mean ADC value of the metastatic nodes was (0.9184±0.0538)×10-3 mm2/sec, lower than the mean value for the benign nodes [(1.2538±0.1145)×10-3 mm2/sec; P=0.005]. Two groups were created according to the mean of the ADC value of hypopharyngeal carcinomas [≤(1.0285±0.0328)×10-3 mm2/sec vs. >(1.0285±0.0328)×10-3 mm2/sec]. The 2-year survival rates of the two groups were 55.6 and 100.0%, respectively (P=0.024). ADC values may aid in distinguishing hypopharyngeal carcinomas from benign lesions and differentiating metastatic lymph nodes of hypopharyngeal squamous cell carcinomas from reactive cervical lymph nodes. In conclusion, mean ADC values may be useful prognostic factors in univariate analysis of hypopharyngeal carcinoma. | Authentic |
Text : MiR-302b is a major microRNA found in human embryonic stem cells and induced pluripotent stem cells. However, its function in gastric cancer progression remains unclear. Quantitative reverse transcription-PCR was performed to detect the expression levels of miR-302b-3p in gastric cancer tissues. MTT, colony formation, and flow cytometer analyses were conducted to explore the function of miR-302b-3p in MKN-45/SGC-7901 cells. A dual-luciferase reporter was used to validate the bioinformatics-predicted target gene of miR-302b-3p. Western blotting and RNA interference were used to evaluate the expression of the AKT signaling pathway and determine the mechanisms underlying miR-302b-3p-induced anti-tumor effects. MiR-302b-3p expression was decreased in gastric cancer tissues and cell lines. Enforced expression of miR-302b suppressed cell proliferation and cell cycle G1-S transition and induced apoptosis. IGF-1R was found to be a direct target of miR-302b-3p, and silencing of IGF-1R resulted in the same biological effects as those induced by miR-302b-3p overexpression in gastric cancer cells. Importantly, both overexpression of miR-302b-3p and silencing of IGF-1R decreased AKT phosphorylation, which modulated AKT related cell cycle regulators (cyclin A2, cyclin D1, CDK2, and CDk6) and apoptotic protein Bax/Bcl-2. These results indicate the tumor suppressor role of miR-302b-3p in the pathogenesis of gastric cancer. | Authentic |
Text : Tumor necrosis factor-alpha (TNF-α) plays an important role in autoimmune diseases. Previous studies have investigated the association of TNF-α-238G/A (rs361525) and -308G/A (rs1800629) polymorphisms with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, no agreed conclusion had been made. Therefore, this meta-analysis was conducted to assess the associations of TNF-α-238G/A and -308G/A polymorphisms with RA and SLE risk. A systematic search was conducted in commonly used databases. Meta-analysis was performed by STATA12.0. A total of 43 studies were included. In the overall population, the TNF-α-238A allele was observed to be a protective factor for RA (A vs G: OR=0.75, 95%CI=0.57-0.99, P=0.040) and the TNF-α-308A allele was found to be a risk factor for SLE (A vs G: OR=1.78, 95%CI=1.45-2.19, P<0.001). However, no evidence of association was found between TNF-α-238 G/A polymorphism and SLE nor between -308G/A and RA. In the subgroup analysis, TNF-α-308A allele played a pathogenic role for RA in Latin Americans (A vs G: OR=1.46, 95%CI=1.15-1.84, P=0.002) and for SLE in Latin Americans (A vs G: OR=2.12, 95%CI=1.32-3.41, P=0.002) and Europeans (A vs G: OR=2.03, 95%CI=1.56-2.63, P<0.001), while it played a protective role for RA in Asians (A vs G: OR=0.54, 95%CI=0.32-0.90, P=0.017). No significant association was found between TNF-α-308G/A and SLE susceptibility in Africans and Asians. This meta-analysis demonstrated that TNF-α-238A was associated with decreased risk of RA rather than SLE, while -308G/A polymorphism was associated with SLE rather than RA. Stratification analysis indicated that different ethnicities would have different risk alleles. | Authentic |
Text : Poly(ADP-ribose) polymerase 3 (PARP3) is the third member of the PARP family that catalyze a post-translational modification of proteins to promote, control or adjust numerous cellular events including genome integrity, transcription, differentiation, cell metabolism or cell death. In the late years, PARP3 has been specified for its primary functions in programmed and stress-induced double-strand break repair, chromosomal rearrangements, transcriptional regulation in the zebrafish and mitotic segregation. Still, deciphering the therapeutic value of its inhibition awaits additional investigations. In this review, we discuss the newest advancements on the specific functions of PARP3 in cancer aggressiveness exemplifying the relevance of its selective inhibition for cancer therapy. | Authentic |
Text : Downregulation of microRNA-590-3p (miR-590-3p) is a frequently occurring, nonphysiological event which is observed in several human cancers, especially breast cancer. However, the significance of miR-590-3p still remain unclear in the progression of this disease. This study explored the role of miR-590-3p in apoptosis of breast cancer cells. Gene expression of miR-590-3p, Sirtuin-1 (SIRT1), Bcl-2 associated X protein (BAX), and p21 was evaluated with real-time polymerase chain reaction (PCR) and SIRT1 protein expression was assessed by Western blot analysis in breast cancer cell lines. Bioinformatics analysis and luciferase reporter assay were used to evaluate targeting of SIRT1 messenger RNA (mRNA) by miR-590-3p. Cells were transfected with miR-590-3p mimic and inhibitor and their effects on the expression and activity of SIRT1 were evaluated. The effects of miR-590-3p upregulation on the acetylation of p53 as well as cell viability and apoptosis were assessed by Western blot analysis, WST-1 assay, and flow cytometry, respectively. miR-590-3p expression was considerably downregulated in breast cancer cells which was accompanied by upregulation of SIRT1 expression. SIRT1 was recognized as a direct target for miR-590-3p in breast cancer cells and its protein expression and activity was dramatically inhibited by the miR-590-3p. In addition, there was an increase in p53 and its acetylated form that ultimately led to upregulation of BAX and p21 expression, suppression of cell survival, and considerable induction of apoptosis in breast cancer cells. These findings suggest that miR-590-3p exerts tumor-suppressing effects through targeting SIRT1 in breast cancer cells, which makes it a potential therapeutic target for developing more efficient treatments for breast cancer. | Authentic |
Text : The poor prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is primarily due to the invasive and metastatic behaviors of this disease. Laminin‑332 (LM‑332) is a key component of the basement membrane barrier, and is associated with tumor metastasis. The present study provides evidence towards the potential function of LM‑332 in carcinoma, indicating the distinct roles of the three LM‑332 subunits (α3, β3 and γ2) in cell proliferation, migration, invasion, apoptosis and the epithelial‑to‑mesenchymal transition (EMT) in cancer. The roles of the α3, β3 and γ2 subunits in the malignant biological behavior of PDAC were investigated in the present study. It was revealed that the α3, β3 and γ2 subunits were upregulated in PDAC. Inhibition of all LM‑332 subunits abrogated the tumorigenic outcomes, which included cell proliferation, apoptosis, invasion, migration and EMT <em>in vitro</em>. However, the three LM‑332 subunits had different degrees of effects on biological behavior. It was observed that LAMA3 (α3) had a stronger effect on cell proliferation, migration and invasion. In addition, LAMB3 (β3) knockdown significantly increased E‑cadherin levels and decreased vimentin levels, indicating that LAMB3 was associated with EMT. Likewise, LAMC2 (γ2) mediated proliferation, apoptosis, invasion and migration. However, small interfering (si)‑LAMC2 promoted the progression of EMT, which was the opposite effect to that of si‑LAMB3. The LM‑332 subunits (α3, β3 and γ2) may be novel therapeutic targets of PDAC in the future. | Authentic |
Text : The liver function index can predict the prognosis of hepatocellular carcinoma and many other non-neoplastic diseases. We aimed to determine whether the preoperative albumin-bilirubin (ALBI) grade could predict the prognosis of patients with gastric cancer (GC). Data of 243 patients with GC who underwent radical resection were collected retrospectively. Patients were divided into the high ALBI (>-2.34) and low ALBI (≤-2.34) grade groups. Overall survival was analyzed between the two groups using the Kaplan-Meier curves. Univariate and multivariate analyses identified the independent factors associated with postoperative complications and overall survival. The postoperative complication rates were higher in the high ALBI grade group than in the low ALBI grade group (P=0.005). The high ALBI grade group also had worse overall survival (P<0.001), especially TNM stage II-III patients (stage II, P=0.043; stage III, P<0.001). In the high ALBI grade group, patients with TNM stage III not undergoing chemotherapy had significantly worse survival times (P=0.001). High ALBI grade (P=0.032), Charlson score of 1-2 (P=0.007), and laparotomy surgery (P=0.045) were independent risk factors for postoperative complications. High ALBI grade (P=0.005), age ≥70 years (P=0.002), nutritional risk screening score 2002 score of 5-6 (P=0.019), tumor located in the cardia (P=0.020), diffuse tumor (P<0.001), and TNM stage III (P<0.001) were independent risk factors for overall survival. Preoperative ALBI grade could predict postoperative complications and overall survival of patients with GC, especially those with TNM stages II-III. This grading method has the advantages of preoperative availability, simplicity, and objectivity and aids in improving preoperative prognosis prediction and in achieving better outcomes of postoperative chemotherapy. | Authentic |
Text : The negative association between Alzheimer's disease (AD) and cancer suggests that susceptibility to one disease may protect against the other. When biological mechanisms of AD and cancer and relationship between them are understood, the unsolved problem of both diseases which still touches the growing human population could be overcome. Actual information about biological mechanisms and common risk factors such as chronic inflammation, age-related metabolic deregulation, and family history is presented here. Common signaling pathways, e.g., p53, Wnt, role of Pin1, and microRNA, are discussed as well. Much attention is also paid to the potential impact of chronic viral, bacterial, and fungal infections that are responsible for the inflammatory pathway in AD and also play a key role to cancer development. New data about common mechanisms in etiopathology of cancer and neurological diseases suggests new therapeutic strategies. Among them, the use of nilotinib, tyrosine kinase inhibitor, protein kinase C, and bexarotene is the most promising. | Authentic |
Text : The ATM and Rad3-related (ATR)/checkpoint kinase 1 (Chk1) pathway plays a pivotal role in DNA damage sensor and modulating homologous recombination. Recently, emerging evidence demonstrated that Chk1 phosphorylation was associated with chemotherapy and radiotherapy resistance. In this study, we explored the effect of ATR/Chk1 pathway on regulating lapatinib sensitivity in human epidermal growth factor receptor-2 (HER2)-positive gastric cancer cell lines. We selected two HER2-positive gastric cancer cell lines, and NCI-N87 cells exhibited higher sensitivity than MKN7 cells. Application of lapatinib inhibited phosphorylated HER2 and EGFR and the formation of epidermal growth factor receptor (EGFR)/HER2 complex in both cells. In NCI-N87 cells, lapatinib induced G1 arrest and reduced Chk1 phosphorylation through inhibiting the expression of DNA topoisomerase 2-binding protein 1 (TopBP1). While in MKN7 cells, no significant cell cycle transition was found and phosphorylated Chk1 was mildly upregulated. Inhibition of Chk1 phosphorylation enhanced the lapatinib sensitivity of MKN7 cells, which was shown by potentiated anti-proliferative effect, G1 arrest, downregulation of phosphorylated AKT and ERK along with aggravated DNA damage. In addition, increased Chk1 phosphorylation in NCI-N87 cells attenuated lapatinib-induced anti-proliferative effect and G1 arrest, and abrogated reduced phosphorylated AKT and ERK. Taken together, our study provides a novel mechanism for regulating lapatinib sensitivity in HER2 positive gastric cancer cells, suggesting a new strategy in clinical treatment. | Authentic |
Text : Gastric cancer presents as a complex solid tumor and is the third leading cause of global cancer‑associated mortality. The genetic alterations in gastric cancer remain unclear and deserve further investigation. Mining The Cancer Genome Atlas gastric adenocarcinoma dataset identified a frequent loss of the zinc finger and BTB domain containing 7A (ZBTB7A) gene locus and a significant correlation between low ZBTB7A expression and poor patient survival. ZBTB7A belongs to the POZ/BTB and Kruppel transcription factor family. In the present study, overexpression of ZBTB7A in a gastric cancer cell line induced cell cycle arrest at the S phase. Upregulation of ZBTB7A also promoted apoptosis and repressed cell migration. The results of the present study indicated that ZBTB7A functions as a tumor suppressor in gastric cancer cells. Understanding the role of ZBTB7A in gastric cancer may provide important clinical insight for treatment. | Authentic |
Text : Colorectal cancer (CRC) is one of the important malignancies that result in cancer-related deaths worldwide. Multiple lines of evidence have indicated that different responses to therapy in CRC cells led to the failure of the current therapies. Hence, identification of the underlying cellular and molecular pathways involved in the emergence of different responses from CRC cells could contribute to finding and designing new therapeutic platforms to overcome the present limitations. Among the various targets involved in CRC pathogenesis, microRNAs (miRNAs) have key roles in many signaling pathways that are associated with the initiation and progression of CRC. Increasing evidence has confirmed that miRNAs as epigenetic regulators could play critical roles in the response (resistance or sensitivity) to therapy. Cancer stem cells are well-known players in resistance to therapy in CRC. They have been shown to play significant roles via inhibition and activation of many miRNA networks. Hence, miRNAs could be involved in the resistance and sensitivity of therapy in CRC cells via affecting different mechanisms, such as activation of cancer stem cells. Here, we summarized the role of various miRNAs in response to therapy of CRC cells. Moreover, we highlighted the roles of these molecules in the function of cancer stem cells, which are known as important players in the resistance to therapy in CRC. | Authentic |
Text : Identification of druggable vulnerabilities is a main objective in triple-negative breast cancer (TNBC), where no curative therapies exist. Gene set enrichment analyses (GSEA) and a pharmacological evaluation using a library of compounds were used to select potential druggable combinations. MTT and studies with semi-solid media were performed to explore the activity of the combinations. TNBC cell lines (MDAMB-231, BT549, HS-578T and HCC3153) and an additional panel of 16 cell lines were used to assess the activity of the two compounds. Flow cytometry experiments and biochemical studies were also performed to explore the mechanism of action. GSEA were performed using several data sets (GSE21422, GSE26910, GSE3744, GSE65194 and GSE42568), and more than 35 compounds against the identified functions were evaluated to discover druggable opportunities. Analyses done with the Chou and Talalay algorithm confirmed the synergy of dasatinib and olaparib. The combination of both agents significantly induced apoptosis in a caspase-dependent manner and revealed a pleotropic effect on cell cycle: Dasatinib arrested cells in G0/G1 and olaparib in G2/M. Dasatinib inhibited pChk1 and induced DNA damage measured by pH2AX, and olaparib increased pH3. Finally, the effect of the combination was also evaluated in a panel of 18 cell lines representative of the most frequent solid tumours, observing a particularly synergism in ovarian cancer. Breast cancer, triple negative, dasatinib, olaparib, screening. | Authentic |
Text : To explore the role of HOTAIR in the pathogenesis of adrenocortical carcinoma (ACC) and its underlying mechanism. Differentially expressed lncRNA (HOTAIR) in ACC was screened out from the GEO database. The survival analysis and ROC curve were performed according to HOTAIR expressions in ACC patients. The correlation between HOTAIR expression and clinical information of ACC patients was analyzed by chi-square test. The univariate and multivariate COX regression analysis was carried out to analyze the relationship between HOTAIR expression, disease-free survival (DFS) and overall survival (OS) of ACC patients. We then detected HOTAIR expression in 77 ACC tissues and 30 normal tissues by qRT-PCR (quantitative Real-time polymerase chain reaction). ACC cell lines were further screened out for the following in vitro experiments. After altering HOTAIR expression in ACC cells by plasmid transfection, proliferation and cell cycle were detected by Cell Counting Kit-8 (CCK-8) and colony formation assay, respectively. Finally, Western blot was utilized to detect expressions of cell cycle-related genes in ACC cells. HOTAIR was overexpressed in ACC tissues than that of normal tissues. HOTAIR expression was remarkably increased in ACC with T3 and T4 stage than that of T1 and T2 stage. Moreover, HOTAIR expression was remarkably increased in ACC with stage III and IV than that of stage I and II. HOTAIR was an independent prognostic factor for DFS and OS of ACC patients. For in vitro experiments, inhibited proliferation and arrested cell cycle were observed in H295R cells transfected with si-HOTAIR. Opposite results were obtained after SW-13 cells were transfected with HOTAIR overexpression plasmid. Furthermore, expressions of cell cycle-related genes, including Cyclin D1, p-Rb and p-GSK3β were remarkably decreased after HOTAIR knockdown. We demonstrated for the first time that HOTAIR is overexpressed in ACC and is a prognostic risk factor in ACC patients. HOTAIR participates in the development and progression of ACC via shortening cell cycle and promoting proliferation of ACC cells. | Authentic |
Text : In order to explore the imaging manifestations and pathological characteristics of spine tumors, this article explores the clinical diagnosis and treatment methods through multi-sample case analysis with the support of imaging, and proposes a targeted treatment method that uses a special PVP needle with a beveled puncture surface for puncture. Moreover, this article uses the supporting PVP syringe for bone cement injection, develops a health status questionnaire, and adopts a scoring method for comprehensive assessment. The purpose of this article is to show that through the combination of preoperative radiotherapy and postoperative bracing, bone cement injection to treat vertebral tumors can immediately obtain satisfactory pain relief. Finally, through case analysis and image performance, we can see that the method proposed in this article has a certain effect. | Authentic |
Text : Considering the resistance of papillary thyroid cancer (PTC) 131I therapy, this study was designed to find a solution at molecular respect. By probing into lncRNA-NEAT1/miR-101-3p/FN1 axis and PI3K/AKT signaling pathway, this study provided a potential target for PTC therapy. 131I-resistant cell lines were established by continuous treatment with median-lethal 131I. Bioinformatic analysis was applied to filtrate possible lncRNA/miRNA/mRNA and related signaling pathway. Luciferase reporter assay was employed in the verification of the targeting relationship between lncRNA and miRNA as well as miRNA and mRNA. MTT assay and flow cytometry assay were performed to observe the impact of NEAT1/miR-101-3p/FN1 on cell viability and apoptosis in radioactivity iodine (RAI)-resistant PTC cell lines, respectively. Western blot and qRT-PCR were conducted to measure the expression of proteins and mRNAs in RAI-resistant PTC tissues and cells. Meanwhile, endogenous PTC mice model were constructed, in order to verify the relation between NEAT1 and RAI-resistance in vivo. NEAT1 was over-expressed in RAI-resistant PTC tissues and cell lines and could resist RAI by accelerating proliferation accompanied by suppressing apoptosis. It indicated that overexpressed NEAT1 restrained the damage of RAI to tumor in both macroscopic and microcosmic. Besides, NEAT1/miR-101-3p exhibited a negative correlation by directly targeting each other. The expression of FN1, an overexpressed downstream protein in RAI-resistance PTC tissues, could be tuned down by miR-101-3p, while the decrease could be restored by NEAT1. In conclusion, both in vitro and in vivo, NEAT1 suppression could inhibit 131I resistance of PTC by upregulating miR-101-3p/FN1 expression and inactivated PI3K/AKT signaling pathway both in vitro and in vivo. | Authentic |
Text : Carcinoma cells that have acquired drug resistance often exhibit cross-resistance to various other cytotoxic stimuli. Here, we investigated the effects of ursodeoxycholic acid (UDCA), a gastrointestinal tumor-suppressor, on a cisplatin‑resistant SNU601 gastric cancer subline (SNU601/R). While other anticancer drugs, including L-OHP, etoposide, and death ligand TRAIL, had minimal effects on the viability of these resistant cells, they were sensitive to UDCA. The UDCA‑induced reduction in the viability of the SNU601/R cells was accomplished through autophagy while the primary means of cell death in the parental SNU601 cells (SNU601/WT) was apoptosis. Previously, we demonstrated that the UDCA-triggered apoptosis of gastric cancer cells was regulated by a cell surface death receptor, TRAIL-R2/DR5, which was upregulated and re-distributed on lipid rafts. The UDCA stimulation of TRAIL-R2/DR5 also occurred in the SNU601/R cells despite the lack of apoptosis. In the present study, we found that CD95/Fas, another cell surface death receptor, was also translocated into lipid rafts in response to UDCA although it was not involved in the decrease in cell viability. Specifically, raft relocalization of CD95/Fas was triggered by UDCA in the SNU601/WT cells in which apoptosis occurred, but not in the SNU601/R cells where autophagic death occurred. Notably, UDCA reduced ATG5 levels, an essential component of autophagy, in the SNU601/WT, but not in the SNU601/R cell line. Moreover, in CD95/Fas-silenced SNU601/WT cells, UDCA did not decrease ATG5 levels and induced autophagic cell death rather than apoptosis. These results imply that raft‑distributed CD95/Fas may support UDCA-induced apoptosis via downregulation of ATG5 levels, preventing the autophagic pathway. Taken together, these results suggest that UDCA induces both apoptotic and autophagic cell death depending on the intracellular signaling environment, thereby conferring the advantage to overcome drug resistance through apoptotic defects. | Authentic |
Text : Non-small cell lung cancer (NSCLC) is one of the major causes of morbidity and mortality worldwide. We aimed to investigate the role of N6-methyladenosine (m6A) methyltransferase-like 3 (METTL3) regulating microRNA-1246 (miR-1246) in the progression of NSCLC by targeting paternally expressed gene 3 (PEG3). METTL3, miR-1246, and PEG3 expression in tissues was assessed, and the predictive role of METTL3 in prognosis of patients with NSCLC was detected. NSCLC cells were relatively treated with altered expression of METTL3, miR-1246, or PEG3 to measure their roles in the proliferation, migration, invasion, apoptosis, and in vivo growth of the NSCLC cells. The RNA m6A level was determined, and the targeting relationship between miR-1246 and PEG3 was confirmed. Our results revealed that METTL3 and miR-1246 were upregulated, whereas PEG3 was downregulated in NSCLC tissues. METTL3 knockdown or PEG3 overexpression in NSCLC cells suppressed malignant behaviors of NSCLC cells. METTL3 affected the m6A modification of miR-1246, thus upregulating miR-1246 and miR-1246-targeted PEG3. The elevation of PEG3 reversed the effects of miR-1246 upregulation on NSCLC cells. This study revealed that m6A methyltransferase METTL3 affects the m6A modification of miR-1246, thus upregulating miR-1246 to promote NSCLC progression by inhibiting PEG3. | Counterfeit |
Text : Patients with aggressive urothelial cell carcinoma (UCC) that undergo radical cystectomy or nephroureterectomy exhibit markedly high rates of disease recurrence and mortality. To select appropriate adjuvant thxerapies in addition to radical surgery, the identification of predictive prognostic markers for UCC patients is required. The aim of the present study was to identify such markers, by evaluating the association of UCC complement component 5 (C5) fragment a (C5a)receptor (C5aR) expression, detected using immunohistochemistry, with clinicopathological parameters and survival outcomes of UCC patients. The results revealed that C5aR was expressed in cancer cells, particularly at the invasive front, but not in noncancerous urothelial cells or adjacent cells. The UCC C5aR-positive rate of patients treated with radical surgeries was 73% (38/52) and the rate was 83% (20/24) at stages I-II of disease. No correlation between C5aR expression and any of clinicopathological parameters, which included gender, tumor location, World Health Organization grade, T stage, vessel invasion and stage of disease, was identified. However, univariate and multivariate analyses revealed that C5aR-positive UCC patients exhibited significantly lower overall survival rates [hazard ratio (HR), 3.14; 95% confidence interval (CI), 1.03-9.60; P=0.035 and HR, 3.92; 95% CI, 1.15-13.4; P=0.029, respectively] and 5-year survival rates (0.42 vs. 0.83) compared with C5aR-negative UCC patients. Furthermore, 5-year survival and disease-specific survival rates were lower in patients with C5aR-positive UCC (0.51; 95% CI, 0.30-0.71) than patients with C5aR-negative UCC (0.83; 95% CI, 0.62-1.00). These results indicate that UCC C5aR expression is predictive of poor patient outcomes and thus may lead to the appropriate selection of adjuvant therapies at earlier UCC stages, which could improve patient prognosis. | Authentic |
Text : Recent evidence has suggested the important implications of microRNAs (miRNAs) in the processes of proliferation and tissue remodeling in endometriosis (EMS). We therefore aim to determine the role of miR-202-3p in the pathophysiology of EMS and its underlying mechanisms. Experimental endometriosis was induced in ovariectomized mice implanted with a slow-release 17-β estradiol capsule. Eutopic endometrial stromal cells (euESCs) were isolated and assayed for proliferative, invasive and apoptotic properties by EdU staining, Transwell assays, and flow cytometry. The invasive and apoptotic features in the endometrium of mice with EMS in vivo were evaluated by using immunohistochemical staining and TUNEL assays. miR-202-3p was observed to be downregulated in the endometrial tissues of EMS patients. MiR-202-3p was also found to target YAP1 which resulted in reduced euESC proliferation and invasion and increased apoptosis. YAP1 was able to phosphorylated STAT3 which consequently upregulated S100A6 to promote the proliferative and invasive abilities of euESCs. MiR-202-3p was thereby proposed to act as an inhibitor of proliferation and tissue damage in the in vivo setting of EMS, its effects however, were able to be counteracted byS100A6, which reversed the effects of miR-202-3p on tissue injury and cell proliferation. Our data together evidenced that miR-202-3p targeted YAP1 to reduce STAT3-mediated S100A6 whereby preventing the progression of EMS. | Counterfeit |
Text : DNA methylation is a physiologically epigenetic alteration that happens when a methyl group is introduced to a CpG dinucleotide in the gene-regulating sequence of DNA. However, the majority of oral cancers have a well-defined precancerous stage; there are few clinical and morphological parameters for detecting and signalling the progression of precancerous to malignant tumours. DNA methylation forms are dynamic and reversible, allowing them to adjust to environmental or therapeutic changes. We did an extensive investigation to compile the data supporting aberrant DNA methylation forms as a possible biomarker for prediction. According to two longitudinal studies, p16 hypermethylation was considerably higher in precancerous lesions that progressed to cancer than in lesions that shrank. Most of the studies examined for this study were tiny cross-sectional research with scant validation and inadequately specified control groups. Existing evidence suggests that DNA methylation sequences can be relevant as a diagnostic biomarker for OPS development; however, sample size and research design restrictions make it difficult to draw definitive conclusions. Strong studies, including extensive epigenome-wide methylation scans of OPS with longitudinal monitoring, are necessary in this study in order to corroborate the recently discovered signals and discover new risk loci and disease progression molecular pathways. | Authentic |
Text : To investigate the effect of BCL6 on methotrexate-resistant children with acute B lymphoblastic leukemia (B-ALL) and its underlying mechanism. Bone marrow samples of B-ALL children diagnosed at The Children & Women's Healthcare of Laiwu City from June 2014 to February 2017 were collected. Subjects were assigned into methotrexate-resistant group (n=8) and non-resistant group (n=32) according to the follow-up outcome. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) was performed to detect expressions of BCL6 and E-cadherin in bone marrow tissues. Cell cycle and apoptosis of methotrexate-resistant B-ALL cells (BALL-1/MTXR cells) were detected after overexpression or inhibition of BCL6, respectively. Western blot was performed to determine the protein levels of E-cadherin and BCL6. The direct binding of BCL6 in the ZEB1 promoter region was verified by the ChIP (chromatin immunoprecipitation) assay. QRT-PCR showed a higher BCL6 expression in bone marrow samples of methotrexate-resistant group than that of the non-resistant group. Moreover, BCL6 was upregulated in BALL-1/MTXR cells than that of untreated B-ALL cells. After knockdown of BCL6 expression, we observed a decreased IC50, increased apoptosis, and arrested the cell cycle in BALL-1/MTXR cells. In addition, increased expression of E-cadherin was found in BALL-1/MTXR cells, which could be reversed by ZEB1 overexpression. ChIP assay suggested that BCL6 bound to the promoter region of ZEB1, so as to promote ZEB1 expression. BCL6 is overexpressed in the bone marrow of methotrexate-resistant children with B-ALL, which is capable of attenuating the sensitivity of B-ALL to methotrexate via promoting ZEB1 expression. | Authentic |
Text : Oral squamous cell carcinoma (OSCC) is a common cancer especially young people in the world. The long non-coding RNA Fer-1-like protein 4 (FER1L4) has been reported to be closely associated with the progression of various human cancers. However, the role of FER1L4 in OSCC remains unclear. The expression level of FER1L4 in OSCC tissues and cancer cell lines was detected by using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was evaluated by cell counting kit-8 (CCK-8) assay and EdU staining assay. Cell invasion and migration were evaluated by Transwell assay. Cell apoptosis was detected by flow cytometry. Luciferase reporter assay was performed to determine the targeting relationship between FER1L4, miR-133a-5p and Prx1. The protein expression of Prx1 was detected by Western blot. In addition, a xenograft tumor model in vivo was constructed to confirm the function of FER1L4. FERIL4 was significantly upregulated in OSCC tissues and cancer cell lines. Moreover, high level of FER1L4 predicted a poor prognosis of OSCC patients. Silencing of FER1L4 not only significantly inhibited cell growth, invasion, migration and induced apoptosis in SCC-9 and HN4 cells in vitro, but also effectively suppressed the tumorigenesis of OSCC cells in vivo. Knockdown of FER1L4 significantly enhanced the expression of miR-133a-5p by sponging it, and then downregulated Prx1 expression. Our study elucidated a new mechanism of lncRNA FER1L4 that promoting OSCC progression by directly targeting miR-133a-5p/Prx1 axis and provided novel therapeutic targets for OSCC. | Authentic |
Text : Background: Previous studies have indicated that younger age is consistently associated with high levels of fear of cancer recurrence (FCR), anxiety and depression. However, the associations among these variables in adolescent and young adult (AYA) cancer patients are not clear. This study explores the prevalence and correlates of FCR, anxiety and depressive symptoms in Chinese AYA cancer population. Methods: This is a cross-sectional study that includes 249 patients aged between 15 and 39 yrs at the time of cancer diagnosis. Patient's sociodemographic, clinical as well as psychological characteristics were collected by an information sheet, the Fear of Progression Questionnaire-Short Form (FoP-Q-SF), General Anxiety Disorder Questionnaire (GAD-7) and Patient Health Questionnaire (PHQ-9). Descriptive statistics and multivariate analyses were conducted. Results: Eighty-nine (35.74%) patients experienced dysfunctional level of FCR, eighty-two (32.93%) patients experienced anxiety symptoms and ninety-six (38.55%) reported depressive symptoms. In multivariate analyses, being single, pessimistic, having more concurrent stressful life events and physical comorbidity were independently associated with higher FCR, anxiety and depressive symptoms. Patients who were not engaging in radiotherapy were more likely to report higher anxiety level. Conclusion: FCR, anxiety and depressive symptoms are frequently reported problems among AYA cancer patients. Age-appropriate and flexible psychological interventions are needed for this high-risk population. | Authentic |
Text : Long non-coding RNA (lncRNA) is a kind of important molecules involved in the formation of immune landscape in tumor microenvironment. However, there are few studies on the relationship between lncRNA and immunomodulatory regulation of hepatocellular carcinoma (HCC). In this study, we combined with single cell transcriptome sequencing and TCGA data to analyze the relationship between lncRNA MIAT and immune cells in HCC. TIMER database analysis indicated that the expression of MIAT in HCC was negatively correlated with tumor purity, positively correlated with the number of immune cells such as B cells, T lymphocytes and macrophages, and positively correlated with the expression of immune checkpoint molecules such as PD-1, PD-L1 and CTLA4. Analysis of single cell sequencing data of immune cells in HCC showed that MIAT was mainly distributed in tumor, and enriched in FOXP3+CD4+T cells and PDCD1+CD8+, GZMK+CD8+T cells, indicating that MIAT may be involved in the immune escape process of HCC. Besides, through the construction of transcription factor (TF) regulatory network, MIAT-TF-mRNA, we found that the interaction of MIAT and TFs may affect the immune microenvironment of LIHC by regulating the expression of target genes JAK2, SLC6A6, KCND1, MEIS3 or RIN1; LncMAP and CARE analysis showed that MIAT was highly related to the sensitivity of many anticancer drugs, especially sorafenib. In addition, the effect of MIAT on PD-L1 and its relationship with sorafinib were verified in clinical specimens and cells. This study made a meaningful attempt to reveal the immune escape mechanism and to find the effectiveness of targeted drugs in patients with HCC. | Authentic |
Text : Breast cancer is a highly harmful malignancy, which often causes great distress to patients and seriously affects their physical and mental health. Breast cancer causes patients to experience decreased appetite, decreased eating, and indigestion, which in turn leads to malnutrition, body wasting, resistance, immune compromise, progressive anemia, cachexia, and, as a result, severe secondary infections. To investigate the efficacy evaluation of neoadjuvant chemotherapy in breast cancer by MRI, forty-eight subjects treated at the hospital from June 2014 to August 2019 were recruited. After the neoadjuvant chemotherapy, the patients were divided into two groups based on the results of histopathological examination, namely, the ineffective group (n = 14) and the effective group (n = 34). Changes in MRI indicators were compared between the two groups before and after the neoadjuvant chemotherapy. The maximum diameter of lesions decreased significantly after the neoadjuvant chemotherapy than before. The apparent diffusion coefficient (ADC) increased considerably, and the time-intensity curve (TIC) showed a transition from type III to type II/I and from type II to type I. MRI can indicate the maximum diameter of the breast cancer lesion, ADC, and TIC type. Therefore, it can be used to evaluate the efficacy of neoadjuvant chemotherapy for breast cancer and be widely applied in clinical practice. | Authentic |
Text : Interferon-induced transmembrane proteins (IFITMs) are expressed in some types of cancer. However, their precise roles in tumor progression remain unclear. The present study investigated the function of IFITM2 in gastric cancer (GC) progression. A retrospective analysis of a public database and 167 GC patients revealed that IFITM2 expression was upregulated in gastric tumor samples, which was positively correlated with disease progression, more frequent postoperative recurrence, and higher mortality rate. IFITM2 knockdown decreased GC cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition in vitro. We also found that IFITM2 expression was in part induced by insulin-like growth factor (IGF) 1 via IGF1 receptor/signal transducer and activator of transcription 3 signaling. Furthermore, IFITM2 regulated interleukin-6 expression and secretion, which in turn increased IFITM2 expression. Silencing of IFITM2 expression suppressed tumor growth and lung metastasis in vivo. These results suggest that IFITM2 is a novel prognostic biomarker and regulator of GC progression. | Counterfeit |
Text : The clinical efficiency of everolimus, an mammalian target of rapamycin (mTOR) inhibitor, is palliative as sequential or second-line therapy for renal cell carcinoma (RCC). However, the limited response of everolimus in RCC remains uncertain. In the present study, everolimus-resistant RCC models were established to understand the mechanisms and to seek combination approaches. Consequently, the activation of ERK was found to contribute toward everolimus-acquired resistance and poor prognosis in patients with RCC. In addition, the efficacy and mechanism of combination treatment underlying RCC using everolimus and ERK inhibitors was investigated. The ERK inhibitor in combination with everolimus synergistically inhibited the proliferation of RCC cells by arresting the cell cycle in the G1 phase. The combination treatment markedly attenuated the deoxyribonucleoside triphosphate (dNTP) pools by downregulating the mRNA expression of RRM1 and RRM2 through E2F1. The overexpression of E2F1 or supplementation of dNTP rescued the anti-proliferation activity of the everolimus-SCH772984 combination. The antitumor efficacy of combination therapy was reiterated in RCC xenograft models. Thus, the current findings provided evidence that the everolimus-ERK inhibitor combination is a preclinical therapeutic strategy for RCC. | Authentic |