基于生物信息学分析的卵巢癌中miR-4324调控机制的研究

Study on the regulation mechanism of miR-4324 in ovarian cancer based on bioinformatics analysis

目的:利用生物信息学研究微小RNA-4324(miR-4324)在卵巢癌中的表达情况,进一步分析miR-4324在卵巢癌发生、发展中的作用。方法:采用GEO数据库及GEO2R在线工具分析miR-4324在卵巢癌中的表达水平。用TargetScan数据库预测miR-4324的靶基因(TG-miR4324),并与从GEO数据库中筛选出的卵巢癌差异表达基因(DEGs)取交集,获得miR-4324相关性差异靶基因。运用DAVID数据库进行GO及KEGG富集分析,STRING数据库构建蛋白互作(PPI)网络,Cytoscape筛选hub基因,Kaplan-Meier Plotter分析hub基因对预后的影响。结果:卵巢癌组织中miR-4324表达下调。获得TG-miR4324共5292个,其中筛选出290个miR-4324相关性差异靶基因,主要在细胞外基质、细胞黏附性、细胞外基质(ECM)受体的相互作用及癌症相关通路中富集。从miR-4324相关性差异靶基因中筛选出8个hub基因,其中SPSB1、TGOLN2等6个基因表达与卵巢癌患者的总生存期(OS)相关。结论:miR-4324在卵巢癌中表达下调,miR-4324相关性差异靶基因在卵巢癌生物学过程中起重要作用。

Objective:To investigate the expression of microRNA-4324(miR-4324)in ovarian cancer using bioinformatics and to explore its role in the genesis and development of ovarian cancer.Methods:GEO database and GEO2R were used to screen the expression of miR-4324 between normal ovarian tissues and ovarian cancers.Target genes of miR-4324(TG-miR4324)were predicted by TargetScan database.Then,we selected the overlapped genes between differentially expressed genes(DEGs)obtained from GEO database and TG-miR4324.GO and KEGG pathway enrichment analysis were performed on these genes.STRING and Cytoscape were used to construct a protein-protein interaction(PPI)network,and the prognostic effects of hub genes were presented by Kaplan-Meier Plotter.Results:The expression of miR-4324 was down-regulated in ovarian cancer.Five thousand two hundred and ninety-two predicted target genes were identified for miR-4324.Subsequently,two hundred and ninety genes overlapped in TG-miR4324 and DEGs were selected for GO and KEGG pathway enrichment analysis.These genes were significantly enriched in extracellular matrix,cellular adhesion,ECM receptor interaction and pathways in the cancer.Six hub genes including SPSB1 and TGOLN2 were significantly associated with the prognosis of patients with ovarian cancer.Conclusion:The expression of miR-4324 is down-regulated in ovarian cancer.Target genes of miR-4324 play an important role in the biological process of ovarian cancer.