miR-96 enhances the proliferation of cervical cancer cells by targeting FOXO1

MiRNAs affect various biological pathways associated with the development, progression, clinical outcome and treatment response improvement in cervical cancer. This study was performed to evaluate the effects of miRNA 96 on cervical cancer and to clarify the mechanism. Vivo and vitro experiments were conducted in our trial. MiR-96 is upregulated in cervical cancer cell lines and cervical cancer tissues and is correlated with clinical features in cervical cancer patients. Overexpression of miR-96 enhances proliferation of cervical cancer cells, while inhibiting miR-96 reduces the proliferation of cervical cancer cells. Inhibition of miR-96 significantly decreased the percentage of cells in the S phase and increased the percentage of cells in G1/G0 peak in both SiHa and CaSki cells compared with NC cells and decreased the expressions of p21, p27 and cyclin D1. FOXO1 3’-UTR was sub cloned into a luciferase reporter vector and the putative miR-96 binding site in the FOXO1 3’-UTR was mutated. Treated with miR-96 inhibitor consistently enhanced the luciferase activity of the FOXO1 3’-UTR luciferase reporter plasmids in both SiHa and CaSki cells, whereas mutations in the miR-96-binding site abolished the effect. Vivo experiment also support these results. Therefore, inhibition of miR-96 might suppress growth, proliferation of CC cells and promote apoptosis of CC cells both in vitro and in vivo.     

Hepatitis B virus X protein boosts hepatocellular carcinoma progression by downregulating microRNA-137

BackgroundHepatocellular carcinoma (HCC) is a frequent diagnosed malignancy. microRNAs (miRs) are involved in various cellular processes during cancer development. This study attempted to probe the miR-based mechanism in hepatitis B virus X protein (HBx) small interfering RNA (siRNA)-treated HCC cells.MethodsHBx expression in hepatocyte and HCC cells was detected, and cells with highest HBx expression were screened out and transfected with HBx-siRNAs. Then the effect of HBx on HCC cell proliferation was detected. miRs differentially expressed in HBx-siRNA-transfected MHCC97H cells were analyzed and verified. miR-137 methylation was analyzed by bioinformatics, and miR-137 restoration was detected after Aza treatment. Furthermore, miR-137 methylation in MHCC97H cells with HBx knockdown or HBx overexpression was detected by methylation specific PCR. The targeting relationship between miR-137 and Notch1 was verified. Then the gain-and-loss functions of miR-137 or/and Notch1 were performed to estimate their roles in HCC cell proliferation. The effects of HBx-siRNA and overexpressed miR-137 in vivo were observed by tumor xenograft in nude mice and immunohistochemistry.ResultsHBx-siRNA weakened MHCC97H cell proliferation and tumor growth. miR-137 was highly expressed in HBx-siRNA-treated HCC cells and targeted Notch1. HBx knockdown decreased miR-137 methylation and restored miR-137 expression. miR-137 overexpression prevented HCC cell proliferation and tumor growth, while miR-137 downregulation reversed the repressing effects of HBx-siRNA on HCC cell proliferation. Inhibition of Notch1 reversed HCC cell proliferation induced by miR-137 downregulation.ConclusionOverexpression of miR-137 blocks HCC cell proliferation in HBx-siRNA-treated MHCC97H cells by targeting Notch1. This study may offer novel target for HCC treatment.     

CD109 promotes the tumorigenic ability and metastatic motility of pancreatic ductal adenocarcinoma cells

BackgroundAccumulating evidence indicates that CD109, a glycosylphosphatidylinositol-anchored glycoprotein, is highly expressed in human epithelial carcinomas of multiple organs including the pancreas, but its functional role in carcinoma development has not yet been fully clarified. The aim of this study was to investigate the role of CD109 in the malignancy of pancreatic ductal adenocarcinoma (PDAC).MethodsPDAC specimens of 145 cases were immunostained for CD109, and correlations between CD109 expression and clinicopathological conditions were analyzed. CD109 expression in PANC-1 cells, a PDAC-derived cell line, was decreased by siRNA or shRNA and its effect on the malignancy of PANC-1 cells was examined.ResultsSuppression of CD109 expression in PANC-1 cells resulted in reduction of in vitro cell motility and tumorigenicity in xenografts. Based on these results, we investigated the relationship between CD109 expression and metastasis of PDAC using tumor tissue specimens. Among 106 recurrent cases of 145 PDAC, there was a tendency for CD109-positive cases to be accompanied by distant metastasis.ConclusionsCD109 plays a critical role in the promotion of tumorigenic ability and cellular motility relating to metastasis of PDAC cells.     

IL-1β基因多态性与汉族人群抑郁障碍相关性研究

目的:探讨白细胞介素（IL）-1β基因多态性与汉族人群生活事件及抑郁障碍的关系。方法:共纳入重性抑郁障碍患者433例作为病例组，并纳入基本情况相匹配的正常对照者421名作为对照组 。以HAMD-17方法分别评定两组受试者抑郁障碍的严重程度，同时以生活事件量表（LES）对病例组近1年的生活事件进行评定。从被试者静脉血中提取基因组DNA，选取IL-1β基因上3个位点:rs13032029 、rs1143623和rs3917368。采用以基质辅助激光解吸电离飞行时间质谱（MALDI-TOF-MS）进行候选基因多态性位点基因分型。运用SPSS22.0统计软件包进行数据分析。结果:在病例组和对照组中，IL-1 β基因rs13032029位点的基因型频率分别为:CC型28.6%和28.5%，CT型47.3%和52.7%，TT型23.8%和18.5%，差异无统计学意义（?字2=4.028，P=0.258）。在病例组和对照组中，rs1143623位点基因型频 率分别为:CC型36.5%和31.1%，GC型45.3%和51.8%，GG型18.0%和16.6%，差异无统计学意义（?字2=4.29，P=0.232）。在病例组和对照组中，rs3917368位点基因型频率分别为:CC型24.5%和25.4%，CT型 47.6%和46.6%，TT型27.3%和27.6%，差异无统计学意义（?字2=0.302，P=0.960）。3个位点不同基因型患者的HAMD总分、各条目之间的差异没有统计学意义。LES总分及生活事件的多元回归分析差异无统 计学意义。结论:未发现IL-1β基因rs13032029、rs1143623和rs3917368基因多态性与汉族人群生活事件和抑郁障碍的发病存在相关性。     

Identification of differentially expressed metastatic genes and their signatures to predict the overall survival of uveal melanoma patients by bioinformatics analysis

AIM: To identify metastatic genes and miRNAs and to investigate the metastatic mechanism of uveal melanoma (UVM). METHODS: GSE27831, GSE39717, and GSE73652 gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database, and the limma R package was used to identify differentially expressed genes (DEGs). Gene Ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using the DAVID online tool. A comprehensive list of interacting DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and Cytoscape software. The Cytoscape MCODE plug-in was used to identify clustered sub-networks and modules of hub genes from the protein-protein interaction network. GEPIA online software was used for survival analysis of UVM patients (n=80) from the The Cancer Genome Atlas (TCGA) cohort. OncomiR online software was used to find that the miRNAs were associated with UVM prognosis from the TCGA cohort. TargetScan Human 7.2 software was then used to identify the miRNAs targeting the genes. RESULTS: There were 1600 up-regulated genes and 1399 down-regulated genes. The up-regulated genes were mainly involved in protein translation in the cytosol, whereas the down-regulated genes were correlated with extracellular matrix organization and cell adhesion in the extracellular space. Among the 2999 DEGs, five genes, Znf391, Mrps11, Htra3, Sulf2, and Smarcd3 were potential predictors of UVM prognosis. Otherwise, three miRNAs, hsa-miR-509-3-5p, hsa-miR-513a-5p, and hsa-miR-1269a were associated with UVM prognosis. CONCLUSION: After analyzing the metastasis-related enriched terms and signaling pathways, the up-regulated DEGs are mainly involved in protein synthesis and cell proliferation by ribosome and mitogen-activated protein kinase (MAPK) pathways. However, the down-regulated DEGs are mainly involved in processes that reduced cell-cell adhesion and promoted cell migration in the extracellular matrix through PI3K-Akt signaling pathway, focal adhesion, and extracellular matrix-receptor interactions. Bioinformatics and interaction analysis may provide new insights on the events leading up to the development and progression of UVM.