Identification and analysis of core target genes of miR-29b-3p in glioma

Objective:To investigate the core target genes of miR-29b-3p,and analyze the clinical significance of the core target genes in glioma.Methods:Bioinformatics analysis was used to predict and screen the target genes of miR-29b-3p.STRING and Cytoscape software were used to analyze the protein-protein interaction(PPI)of target genes.the differences expression and survival prognosis in glioma were analyzed by GEPIA and CGGA.Independent prognostic factors analyzed by univariate and multivariate Cox proportional hazards regression model.Results:22 target genes of miR-29b-3p were predicted using LinkedOmics,miRDB,miRTarBase,TargetScan,and starbase databases.Through the construction of the PPI network,genes out of the network were removed,and a total of 16 genes were screened for further study of their clinical significance.Based on analysis of GEPIA and CGGA databases,COL2A1,DNMT3A,and DNMT3B were excluded.Through further analysis of the univariate and multivariate Cox proportional hazard regression model,finally identified three core target genes:SERPINH1,LOXL2,CDK6.Conclusion:Bioinformatics analysis showed that miR-29b-3p targeted three core genes such as SERPINH1,LOXL2,and CDK6 in glioma.The expression of these genes was different between brain normal tissues and gliomas,between different grades of tumor,IDH mutation status and 1p/19q codeletion status.Its high expression had adverse effects on overall survival and recurrence-free survival.These core target genes can be used as an independent prognostic factor.

MicroRNA221 Regulates Epithelial-mesenchymal Transition-related Gene Expression and Cell Replication in Glioma Cells

MicroRNAs （miRNAs） are short regulatory RNAs which negatively mediate protein expression and involve in the pathogenesis of different types of human cancers, including glioblastoma. Especially, the expression levels of miP, JqA-221 are highly expressed in many cancers and miRNA-221 exerts its key roles as an oncogene. However, it is unclear whether miRNA-221 could be participated in the regulation of epithelial-mesenchymal transition （EMT）-related gene and protein expression in glioma cells. In this study, the EMT-related gene and protein expression and cell proliferation in glioma cells were evaluated using qRT-PCR, western blotting and cell viability assay. The results showed that miR-221 was over expressed in glioma cells. Moreover, the mRNA expression levels of PTEN and E-cadherin were low expressed in glioma cells. Conversely, the mRNA expression levels of vimentin were over expressed. Further investigation revealed that the expression levels of vimentin and phospho-Akt were dramatically up-regulated in glioma cells, whereas the expression levels of E-cadherin were significantly down-regulated. Taken together, the data suggests that miR-221 regulates the expression of EMT-related gene and cell proliferation in glioma cells. These findings may provide a potential therapeutic target for treatment of glioblastoma.

人脑胶质瘤中microRNA-221的表达及临床意义

目的探讨microRNA-221(miR-221)在胶质瘤中的表达及其与预后的相关性。方法收集不同级别胶质瘤及瘤组织旁正常组织标本,以定量PCR方法检测miR-221的表达。建立受试者工作特征(ROC)曲线,计算ROC曲线下的面积(AUC)来评估miR-221在胶质瘤组织和瘤组织旁正常组织中表达水平的差异。通过Kaplan-Meier法为高表达群体及低表达群体建立生存曲线,并用Log-rank检验评估两组生存曲线的差异。结果miR-221在胶质瘤组织中的表达显著高于正常组织,并且与胶质瘤的病理级别呈正相关。在生存分析中,miR-221高表达的胶质瘤患者预后较差。结论 miR-221可以作为胶质瘤病理级别分类及预后判断的生物学标记物。

MiR-215活化重组人β-连环素蛋白互作蛋白1/β-catenin信号通路促进脑胶质瘤的发展

本刊编委,武汉大学人民医院检验医学中心童永清博士课题组于2015年在《Oncotarget》（2015,6（28）：25024-25033,IF：6.359）发表了题为＂MiR-215,an activator of the CTNNBIP1/β-catenin pathway,is a marker of poor prognosis in human glioma＂的研究论文,主要内容如下：1研究背景和目的：脑部肿瘤超过50%以上为脑胶质瘤,其预后差。miR-215能促进多种恶性肿瘤的生长,

恶性胶质瘤患者预后与微小RNA-221和微小RNA-222表达的关系

目的探讨微小RNA（miRNA）-221和miRNA-222表达与胶质瘤病理分级及胶质瘤患者预后的关系。方法收集手术切除的胶质瘤标本120例，病理学分级I级19例、Ⅱ级31例、Ⅲ级38例、Ⅳ级32例；采用实时聚合酶链反应（Real—timePCR）及荧光原位杂交（FISH）法检测miRNA-221和miRNA-222的表达。对进行标准治疗的胶质瘤患者进行4年随访。结果肿瘤病理级别随miRNA-221和miRNA-222表达的升高而增加，组间比较差异有统计学意义（x2=43．53，P〈0．01）；生存时间随miRNA-221和miRNA-222表达升高而减少，各组间差异有统计学意义（x2=55．63，P〈0．01）。结论miRNA-221和miRNA-222的表达与胶质瘤的病理学分级及预后密切相关，可以作为独立的预后因素。