bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum exosomal miR‐210 as a potential biomarker for clear cell renal cell carcinoma
Authors: Wang Xuegang , Wang Tao , Chen Chenxi , Wu Zhun , Bai Peide , Li Shouchun , Chen Bin , Liu Rongfu , Zhang Kaiyan , Li Wei , Chen Yuedong , Xing Jinchun 
Published: October 2018

AbstractExosomal microRNAs (miRNAs) are suggested to reflect molecular changes occurring in their cells of origin and are potential indicators in the early detection of cancers. This study aimed to determine whether certain exosomal miRNAs from tumor tissue can be used as noninvasive biomarkers for clear cell renal cell carcinoma (ccRCC). Based on ccRCC miRNA expression profiles and the literature, we selected six miRNAs (miR‐210, miR‐224, miR‐452, miR‐155, miR‐21, and miR‐34a) and analyzed their expression in tissues, sera, and serum exosomes through quantitative real‐time polymerase chain reaction in hypoxia‐induced (with CoCl2) renal cell lines. miR‐210, miR‐224, miR‐452, miR‐155, and miR‐21 were upregulated in tumor tissues compared with normal tissues. Serum miR‐210 and miR‐155 levels were higher in patients with ccRCC than in healthy controls (HCs). Furthermore, only exosomal miR‐210 was significantly upregulated in patients with ccRCC than in HCs. Moreover, receiver operating characteristic (ROC) curve analysis revealed an area under the ROC curve of 0.8779 (95% confidence interval, 0.7987‐0.9571) and a sensitivity and specificity of 82.5% and 80.0%, respectively. Moreover, exosomal miR‐210 was upregulated at an advanced stage, and Fuhrman grade and metastasis decreased significantly one month after surgery. Acute hypoxia exposure activates miR‐210 and release of exosomes with upregulated miR‐210 in both normal and tumor RCC cell lines and interferes with vacuole membrane protein 1 mRNA expression, especially in the metastatic ccRCC cell line. In conclusion, Serum exosomal miR‐210 originating from tumor tissue has potential as a novel noninvasive biomarker for the detection and prognosis of ccRCC.
Chemical inhibition of HSP90 inhibits TNF‐α mediated proliferation and induces apoptosis in human rheumatoid arthritis fibroblast‐like synoviocytes
Authors: Yang Bin , Liu Xiangru , Liang Yongqian , Li Yue 
Published: October 2018

AbstractRheumatoid arthritis fibroblast‐like synoviocytes (RAFLS) proliferate abnormally and resist apoptosis. Geldanamycin (GA) and other HSP90 inhibitors have emerged as promising therapeutic agents that inhibited cancer cell growth. In this study, we explored the effects of HSP90 inhibitor, GA, on tumor necrosis factor (TNF)‐α‐induced proliferation and apoptosis of RAFLS, and the underlying mechanism. Human RAFLS was isolated from the knee joints of patients with RA and subjected to TNF‐α treatment in combination of various concentration of GA. We found that GA dose‐dependently inhibited TNF‐α‐induced RAFLS proliferation as measured, but promoted RAFLS apoptosis. Further mechanistic study identified that GA dose‐dependently attenuated TNF‐α‐mediated activation of mitogen‐activated protein kinases (MAPKs) and nuclear factor‐kappa B (NF‐κB) pathways, both of which are involved in TNF‐α‐mediated RAFLS proliferation. Moreover, GA‐induced apoptosis and mitochondrial damage of RAFLS, as evidenced by increased Bax/Bcl‐2 ratio and mitochondrial cytochrome c release, and enhanced cleavages of caspase‐3, caspase‐9, and poly‐(ADP‐ribose) polymerase. Collectively, our results revealed that chemical inhibition of HSP90 by GA suppressed TNF‐α‐induced proliferation of RAFLSs through the MAPK and NF‐κB signaling pathways and induces RAFLS apoptosis via mitochondria‐dependent pathway. These findings demonstrated for the first time that HSP90 inhibition in RAFLS could be therapeutic beneficial for RA.
Identification of potential drugs targeting L,L‐diaminopimelate aminotransferase of Chlamydia trachomatis: An integrative pharmacoinformatics approach
Authors: Sadhasivam Anupriya , Vetrivel Umashankar 
Published: October 2018

AbstractChlamydia trachomatis (C.t) is a gram‐negative obligate intracellular bacteria, which is a major causative of infectious blindness and sexually transmitted diseases. A surge in multidrug resistance among chlamydial species has posed a challenge to adopt alternative drug targeting strategies. Recently, in C.t, L,L‐diaminopimelate aminotransferase (CtDAP‐AT) is proven to be a potential drug target due its essential role in cell survival and host nonspecificity. Hence, in this study, a multilevel precision‐based virtual screening of CtDAP‐AT was performed to identify potential inhibitors, wherein, an integrative stringent scoring and filtration were performed by coupling, glide docking score, binding free energy, ADMET (absorption, distribution, metabolism, and excretion, toxicity) prediction, density functional theory (quantum mechanics), and molecular dynamics simulation (molecular mechanics). On cumulative analysis, NSC_5485 (1,3‐bis((7‐chloro‐4‐quinolinyl)amino)‐2‐propanol) was found to be the most potential lead, as it showed higher order significance in terms of binding affinity, bonded interactions, favorable ADMET, chemical reactivity, and greater stabilization during complex formation. This is the first report on prioritization of small molecules from National Cancer Institute (NCI) and Maybridge data sets (341 519 compounds) towards targeting CtDAP‐AT. Thus, the proposed compound shall aid in effective combating of a broad spectrum of C.t infections as it surpassed all the levels of prioritization.
Retracted: Effects of microRNA‐494 on proliferation, migration, invasion, and apoptosis of medulloblastoma cells by mediating c‐myc through the p38 MAPK signaling pathway
Authors: Xu Xiao‐Heng , Zhang Si‐Jin , Hu Qi‐Bo , Song Xing‐Yu , Pan Wei 
Published: October 2018

AbstractMedulloblastoma (MB) is the most prevalent brain tumor that occurs during childhood and originates from cerebellar granule cell precursors. Based on recent studies, the differential expression of several microRNAs is involved in MB, while the role of microRNA‐494 (miR‐494) in MB remains unclear. Therefore, we conducted this study to investigate the regulative role of miR‐494 in MB cells via the p38 mitogen‐activated protein kinase (MAPK) signaling pathway by mediating c‐myc. In the current study, MB cells were collected and transfected with miR‐494 mimic, miR‐494 inhibitor, siRNA‐
c‐myc, and miR‐494 inhibitor + siRNA‐c‐myc. The expressions of miR‐494, c‐myc, p38 MAPK, B‐cell lymphoma‐2 (Bcl‐2), Bcl‐2‐associated X protein (Bax), interleukin‐6 (IL‐6), metadherin (MTDH), phosphatase and tensin homolog (PTEN) and survivin were determined. Cell proliferation, cell‐cycle distribution, apoptosis, migration, and invasion were evaluated. The results revealed that there was a poor expression of miR‐494 and high expression of
c‐myc in MB tissues.
C‐myc was determined as the target gene of miR‐494. In response to miR‐494 mimic, MB cells were found to have increased Bax and PTEN expressions, as well as cell number in G1 phase and cell apoptosis and decreased
c‐myc, p38 MAPK, Bcl‐2, MTDH, IL‐6, and survivin expression and cell number count in the S phase, cell proliferation, migration, and invasion. In conclusion, the results demonstrated that the upregulation of miR‐494 results in the suppression of cell proliferation, migration, and invasion, while it promotes apoptosis of MB cells through the negative mediation of
c‐myc, which in turn inactivates the p38 MAPK pathway.
Stomatin‐like protein‐2 relieve myocardial ischemia/reperfusion injury by adenosine 5′‐monophosphate‐activated protein kinase signal pathway
Authors: Qiu Zhibing , Chen Xin , Yin Li , Chen Wen , Xu Yueyue , Jiang Ben 
Published: October 2018

AbstractPrevious studies have shown that stomatin‐like protein‐2 (SLP‐2) could regulate mitochondrial biogenesis and function. The study was designed to explore the contribution of SLP‐2 to the myocardial ischemia and reperfusion (I/R) injury. Anesthetized rats were treated with SLP‐2 and subjected to ischemia for 30 minutes before 3 hours of reperfusion. An oxygen‐glucose deprivation/reoxygenation model of I/R was established in H9C2 cells. In vivo, SLP‐2 significantly improved cardiac function recovery of myocardial I/R injury rats by increasing fractional shortening and ejection fraction. SLP‐2 pretreatment alleviated infarct area and myocardial apoptosis, which was paralleled by decreasing the level of cleaved caspase‐3 and the ratio of Bax/Bcl‐2, increasing the content of superoxide dismutase and reducing oxidative stress damage in serum. In addition, SLP‐2 increased the level of ATP and stabilized mitochondrial potential (Ψm). The present in vitro study revealed that overexpression with SLP‐2 reduced H9C2 cells apoptosis, accompanied by an increased level of ATP, the ratio of mitochondrial DNA/nuclear DNA, activities of complex II and V, and decreased the production of mitochondrial reactive oxygen species. Simultaneously, SLP‐2 activated the adenosine 5′‐monophosphate‐activated protein kinase (AMPK) signaling pathway in myocardial I/R injury rats and H9C2 cells. This study revealed that SLP‐2 mediates the cardioprotective effect against I/R injury by regulating AMPK signaling pathway.
Renalase rs10887800 polymorphism is associated with severe pre‐eclampsia in southeast Iranian women
Authors: Teimoori Batool , Moradi‐Shahrebabak Maryam , Rezaei Mahnaz , Mohammadpour‐Gharehbagh Abbas , Salimi Saeedeh 
Published: October 2018

AbstractEvidence has shown that pre‐eclampsia (PE) is associated with an increased level of catecholamines. Renalase is a catecholamine‐metabolizing enzyme, which contributes to the occurrence of hypertension. In the current study, we aimed to assess the relation between two renalase gene (
RNLS) polymorphisms, including rs2576178 at the 5′‐flanking region and rs10887800 at intron 6, near the exon/intron border and PE susceptibility. In this case‐control study, 179 women with PE and 202 normotensive pregnant women were genotyped for
RNLS rs2576178 and rs10887800 polymorphisms by the polymerase chain reaction‐restriction fragment length polymorphism method. There was no association between
RNLS rs10887800 and rs2576178 polymorphisms and PE, neither in the dominant nor in the recessive model. Although there was no association between
RNLS rs10887800 polymorphism and mild PE, this polymorphism was associated with 2.2‐fold higher risk of severe PE in the recessive model (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.2‐4.4;
P = 0.01) but not in the dominant model. The
RNLS rs2576178 and rs10887800 polymorphisms were not associated with PE severity. The
RNLS rs10887800 and rs2576178 GG/GG combined genotypes were associated with 8.4‐ and 16.7‐fold higher risk of PE and severe PE, respectively (OR, 8.4; 95% CI, 1‐71.1;
P = 0.048 and OR, 16.7; 95% CI, 1.6‐167;
P = 0.018). Also, the G‐G haplotype was associated with 1.7‐fold risk of PE and mild PE (OR, 1.7; 95% CI, 1.1‐2.4;
P = 0.009 and OR, 1.7; 95% CI, 1.1‐2.5;
P = 0.02). The
RNLS rs10887800 polymorphism was associated with severe PE. The
RNLS rs10887800 and rs2576178 GG/GG combined genotypes and G‐G haplotype were associated with higher risk of PE.
SIRT1‐ZEB1‐positive feedback promotes epithelial‐mesenchymal transition process and metastasis of osteosarcoma
Authors: Yu Xiao‐Jun , Guo Xin‐Zhen , Li Chao , Chong Yang , Song Tie‐Nan , Pang Jian‐Feng , Shao Ming 
Published: October 2018

AbstractOsteosarcoma is the most common malignant bone cancer that mainly affects children and young adults. Recently, the NAD+‐dependent deacetylase, sirtuin 1 (SIRT1), has been reported to play a key role in the development of malignant tumors. The study aimed to investigate the role of SIRT1 in osteosarcoma and explore its underlying oncogenic mechanisms. The prognostic value of SIRT1 in osteosarcoma was assessed through detection of SIRT1 expression based on osteosarcoma biopsy tissue. Then, to further investigate the effect of SIRT1 in osteosarcoma, osteosarcoma cells were treated with small interfering RNA SIRT1 and overexpressed SIRT1 to detect the cell migration, invasion, and epithelial‐mesenchymal transition (EMT). The levels of SIRT1 expression were significantly higher in osteosarcoma tissues than those in adjacent normal tissues, and the SIRT1 protein level may be coupled with metastatic and poor prognosis risk in patients with osteosarcoma. Moreover, SIRT1 silencing inhibited the migration as well as invasion ability of osteosarcoma cells in vitro, and SIRT1 upregulation reversed those effects. Finally, we found that SIRT1‐ZEB1‐positive feedback enhanced the EMT process and metastasis of osteosarcoma. Altogether, the results of the current study revealed that high levels of SIRT1 might be a biomarker for a high metastatic rate in patients with osteosarcoma, which suggested that inhibition of SIRT1 might be promising for the therapeutics of osteosarcoma.
LncRNA MNX1‐AS1 promotes the progression of cervical cancer through activating MAPK pathway
Authors: Liu Xiang , Yang Qian , Yan Jinyu , Zhang Xiahui , Zheng Meiyun 
Published: October 2018

AbstractLong noncoding RNAs (lncRNAs) have been discovered as significant regulators in a wide range of human cancers. Among them, lncRNA MNX1‐AS1 has been proved to be an oncogene in ovarian cancer and glioblastoma. However, the regulatory mechanism of MNX1‐AS1 in cervical cancer remains to be understood. Therefore, this study planned to explore the role of MNX1‐AS1 in cervical cancer. In the beginning, we found that the expression of MNX1‐AS1 was obviously upregulated in cervical cancer tissues and cell lines. Kaplan‐Meier survival analysis revealed that patients with higher MNX1‐AS1 expression level suffered from shorter overall survival time than those with lower MNX1‐AS1 level. Moreover, by loss‐of‐function and gain‐of‐function assay, the effect of MNX1‐AS1 on cell proliferation and apoptosis was examined on cellular level. Results showed that the proliferation of Hela cells was significantly inhibited and apoptosis enhanced by the transfection of shMNX1‐AS1, while overexpressing MNX1‐AS1 in E6E7 cells presented the contrary results. As for mechanism investigation, it was demonstrated that overexpression of MNX1‐AS1 significantly improved the expression of p‐ERK1/2 and p‐JNK. And the effects of MNX1‐AS1 on cell proliferation and apoptosis would be diminished after inactivating the phosphorylation of either ERK or JNK. Taken together, it was identified that MNX1‐AS1 promoted proliferation and inhibited apoptosis of cervical cancer cells through MAPK pathway.
Hypoxia‐induced regulation of mTOR signaling by miR‐7 targeting REDD1
Authors: Seong Minhyeong , Lee Jihui , Kang Hara 
Published: October 2018

AbstractOxygen is an important factor mediating cell growth and survival under physiological and pathological conditions. Therefore, cells have well‐regulated response mechanisms in the face of changes in oxygen levels in their environment. A subset of microRNAs (miRNAs) termed the hypoxamir has been suggested to be a critical mediator of the cellular response to hypoxia. Regulated in development and DNA damage response 1 (REDD1) is a negative regulator of mammalian target of rapamycin (mTOR) signaling in the response to cellular stress, and is elevated in many cell types under hypoxia, with consequent inhibition of mTOR signaling. However, the underlying posttranscriptional regulatory mechanism by miRNAs that contribute to this hypoxia‐induced reduction in REDD1 expression remain unknown. Therefore, the aim of the current study was to identify the miRNAs participating in the hypoxic cellular response by scanning the 3′‐untranslated region (3′‐UTR) of REDD1 for potential miRNA‐binding sites using a computer algorithm, TargetScan. miR‐7 emerged as a novel hypoxamir that regulates REDD1 expression and is involved in mTOR signaling. miR‐7 could repress REDD1 expression posttranscriptionally by directly binding with the 3′‐UTR. Upon hypoxia, miR‐7 expression was downregulated in HeLa cells to consequently derepress REDD1, resulting in inhibition of mTOR signaling. Moreover, overexpression of miR‐7 was sufficient to reverse the hypoxia‐induced inhibition of mTOR signaling. Therefore, our findings suggest miR‐7 as a key regulator of hypoxia‐mediated mTOR signaling through modulation of REDD1 expression. These findings contribute new insight into the miRNA‐mediated molecular mechanism of the hypoxic response through mTOR signaling, highlighting potential targets for tumor suppression.
MicroRNA‐21 increases the expression level of occludin through regulating ROCK1 in prevention of intestinal barrier dysfunction
Authors: Liu Zhihua , Li Chao , Chen Shihua , Lin Hongcheng , Zhao Huan , Liu Min , Weng Jinsheng , Liu Ting , Li Xiaomei , Lei Chao , Li Chen , Jiang Yanqiong , Moyer Mary Pat , Yin Chunxia , Zhou Xinke 
Published: October 2018

AbstractObjectiveThe aim of this study is to investigate the role of molecular mechanism of microRNA (miR)‐21 on tight junction (TJ)‐proteins and its protective effects on the intestinal barrier.MethodsTJ proteins and target genes expression were analyzed in miR‐21 inhibition and overexpression NCM460 cell lines. To further verify the role of miR‐21, the mmu‐miR‐21 intestinal epithelial conditional knockout (IKO) mice model was established. MiR‐21 expression was detected in clinical specimens of acute stercoral obstruction patients.ResultsRho‐associated protein kinase 1 (ROCK1) were identified as target genes of miR‐21. There is a negative correlation between miR‐21 expression level and TJ proteins levels. TJ protein and ROCK1 were significantly decreased in miR‐21 IKO mice, which presented intestinal inflammation response and intestinal barrier dysfunction (both P < 0.05). Determination of clinical samples showed consistent results with NCM460 cell line and miR‐21 IKO mice.ConclusionsMiR‐21 could be a protective factor of intestinal barrier dysfunction, which promoting the expression of TJ protein by targeting ROCK1 in vivo and in vitro.
Roles for osteocalcin in proliferation and differentiation of spermatogonial cells cocultured with somatic cells
Authors: Solhjoo Somayeh , Akbari Mohammad , Toolee Heidar , Mortezaee Keywan , Mohammadipour Mahshid , Nematollahi‐Mahani Seyed Noureddin , Shahrokhi Amene , Sayadi Mahtab , Rastegar Tayebeh 
Published: October 2018

AbstractSpermatogonial cells (SCs) are key cells for spermatogenesis. These cells are affected by paracrine signals originated from nearby somatic cells, among them Leydig cells have receptors for osteocalcin, a hormone known for exerting positive roles in the promotion of spermatogenesis. The aim of this study was to evaluate roles for osteocalcin on SCs proliferative and differentiation features after coculture with Leydig cells. SCs and Leydig cells were isolated from neonate NMRI offspring mice and adult NMRI mice, respectively. SCs population were then enriched in a differential attachment technique and assessed for morphological features and identity. Then, SCs were cocultured with Leydig cells and incubated with osteocalcin for 4 weeks. Evaluation of proliferation and differentiation‐related factors were surveyed using immunocytochemistry (ICC), Western blot, and quantitative real‐time polymerase chain reaction (PCR). Finally, the rate of testosterone release to the culture media was measured at the end of 4th week. Morphological and flow cytometry results showed that the SCs were the population of cells able to form colonies and to express ID4, α6‐, and β1‐integrin markers, respectively. Leydig cells were also able to express Gprc6α as a specific marker for the cells. Incubation of SCs/Leydig coculture with osteocalcin has resulted in an increase in the rate of expressions for differentiation‐related markers. Levels of testosterone in the culture media of SCs/Leydig was positively influenced by osteocalcin. It could be concluded that osteocalcin acts as a positive inducer of SCs in coculture with Leydig cells probably through stimulation of testosterone release from Leydig cells and associated signaling.
Long noncoding RNA HOTAIRM1 inhibits cell progression by regulating miR‐17‐5p/PTEN axis in gastric cancer
Authors: Lu Ruiqi , Zhao Gang , Yang Yulong , Jiang Zhaoyan , Cai Jingli , Zhang Zhijue , Hu Hai 
Published: October 2018

AbstractObjectivesThis study was conducted to identify the significantly altered long noncoding RNAs (lncRNAs), messenger RNA (mRNA) and pathways in gastric cancer (GC).MethodsWe used microarray analysis to identify differentially expressed lncRNAs and mRNAs, whereas the obviously changed pathways were found by gene set enrichment analysis. The coexpression network of lncRNA and mRNA was constructed by Cytoscape, and their target relationships with miRNAs were predicted by miRcode and TargetScan. qRT‐PCR and Western blot were performed to determine the expression levels of mRNAs and proteins in tissues and cell lines. Dual‐luciferase reporter assay was applied to achieve the determination of the specific target relationships. Cell viability, migration, and apoptosis were detected by MTT assay, wound healing assay and flow cytometry, respectively. Through the xenograft assay, the gastric tumor was implanted into nude mice to investigate the influence of HOTAIRM1 in vivo.ResultsHOTAIRM1 and phosphatase and tensin homolog (PTEN) were both downregulated in GC, whereas miR‐17‐5p was upregulated. Moreover, the PI3K/AKT pathway was found activated in GC. HOTAIRM1 targeted miR‐17‐5p, whereas
PTEN was the downstream target gene of miR‐17‐5p. HOTAIRM1 suppressed proliferation and migration of GC cell line and induced their apoptosis, whereas miR‐17‐5p played the opposite role on GC cell line. HOTAIRM1 also postponed tumor growth in vivo and inhibited the PI3K/AKT pathway in GC.ConclusionsLncRNA HORAIRM1 suppressed the PI3K/AKT pathway in GC and inhibited the progression of GC by serving as a competing endogenous RNA of miR‐17‐5p, mediating the expression of
PTEN.
MiR‐10a functions as a tumor suppressor in prostate cancer via targeting KDM4A
Authors: Mu Haiqi , Xiang Luxia , Li Shaoxun , Rao Dapang , Wang Shuaibin , Yu Kaiyuan 
Published: October 2018

AbstractDeregulation of microRNAs contributes to the abnormal cell growth which is frequently observed in cancer. In the current study, we detected the expression and regulatory relationship between miR‐10a and Lysine‐specific demethylase 4A (KDM4A) to reveal their function in prostate cancer (PCa) progression. We found that miR‐10a levels were significantly decreased in PCa cell lines in comparison with the normal epithelial cell line RWPE‐1. Downregulation of miR‐10a levels was also observed in tumor tissues from PCa patients compared with the adjacent normal tissues. Enhanced expression of miR‐10a inhibited cell proliferation and colony forming capability of PCa cells. In addition, quantitative real‐time polymerase chain reaction and Western blot analysis showed a significant decrease of KDM4A in response to miR‐10a elevation in PCa cells. Using dual luciferase assay, we confirmed that KDM4A was a target gene for miR‐10a. Furthermore, Western blot analysis indicated that miR‐10a overexpression inactivated YAP signaling and suppressed transcription of YAP target genes. Additionally, cell growth arrest and colony forming capacity inhibition induced by miR‐10a overexpression could be reversed by YAP overexpression in PCa cells. More importantly, miR‐10a mimics inhibited PC‐3 tumor growth in nude mice accompanied with a remarkable reduction of KDM4A and YAP expression. In conclusion, our results uncovered a tumor suppressor role of miR‐10a in PCa via negative regulation of KDM4A and its downstream Hippo‐YAP pathway.