多形性胶质母细胞瘤相关miRNAs的鉴定与分析

Identification and Analysis of miRNAs Associated with Glioblastoma Multiforme

目的筛选多形性胶质母细胞瘤(glioblastoma multiforme,GBM)相关的miRNAs并进行生物信息学分析。方法从基因表达数据库(gene expression omnibus,GEO)中下载芯片数据集GSE65626,采用BRB-Array Tools鉴定差异表达miRNAs。利用miRanda和TargetScan在线工具预测差异表达miRNAs的靶基因,然后对靶基因进行基因本体(gene ontology,GO)功能富集分析和通路富集分析,并构建miRNA-Gene互作网络。结果从GBM组织和瘤旁组织之间共筛选出128个差异表达miRNAs,其中61个上调表达,67个下调表达。GO功能富集分析表明差异表达miRNAs的靶基因主要涉及转录调控、信号传导、轴突导向、细胞粘附、细胞增殖与凋亡调控等生物过程。通路富集分析发现靶基因显著富集于磷脂酰肌醇3-激酶(phosphatidylinositol-3-kinase,PI3K)-Akt信号通路、粘着斑、细胞骨架调节、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路、轴突导向等通路。miRNA-Gene互作网络分析鉴定的核心miRNAs有hsa-miR-106b-5p、hsa-miR-195-5p、hsa-miR-5001-5p、hsa-miR-27a-3p、hsa-miR-130a-3p。结论 miRNAs表达异常在人类GBM中发挥着重要作用,为阐明miRNAs在GBM发生发展过程中的分子机制以及开发靶向治疗提供基础。

Objective To screen and analyze the miRNAs associated with glioblastoma multiforme(GBM) in bioinformatics.Methods The microarray dataset GSE65626 was downloaded from the gene expression omnibus(GEO) database,and the BRB-Array Tools was applied to identify the differentially expressed miRNAs.The target genes of differentially expressed miRNAs were predicted using miRanda and TargetScan online tools,then gene ontology(GO) function enrichment and pathway enrichment analyses were conducted based on these target genes.Moreover,the miRNA-Gene interactions network was constructed.Results Atotal of 128 differentially expressed miRNAs were identified between GBM tissue and adjacent normal tissue,of which 61 miRNAs were up-regulated and 67 miRNAs were down-regulated.GO function enrichment analysis showed that target genes of differentially expressed miRNAs mainly involved in biological processes of transcriptional regulation,signal transduction,axon guidance,cell adhesion,regulation of cell proliferation and apoptosis.Pathway enrichment analysis found that target genes were mostly enriched in phosphatidylinositol-3-kinase(PI3 K)-Akt signaling pathway,focal adhesion,regulation of actin cytoskeleton,mitogen-activated protein kinase(MAPK) signaling pathway,and axon guidance.The miRNA-Gene interactions network analysis identified the hub miRNAs such as hsa-miR-106 b-5 p,hsa-miR-195-5 p,hsa-miR-5001-5 p,hsa-miR-27 a-3 p,hsa-miR-130 a-3 p.Conclusion miRNAs dysregulation exerts important roles in human GBM,which provides the foundation for clarifying the molecular mechanism underlying the tumorigenesis and developing targeted therapy for GBM.