miR-203a-3p.1调控VCAN作为胃癌潜在治疗靶点的生物信息学研究

VCAN regulated by miR-203a-3p.1 as a potential therapeutic target for gastric cancer via bioinformatics analysis

目的采用生物信息学技术探讨胃癌发生及进展的机制。方法采用GEO分析数据集GSE54129中胃癌组织标本与正常胃黏膜组织标本的差异表达基因(DEGs),然后用DAVID数据库对DEGs进行富集分析,STRING构建蛋白质相互作用(PPI)网络,Cytoscape软件可视化,MCODE和cytoHubba筛选关键基因,并在GEPIA数据库及胃癌组织标本中验证关键基因,之后用Target Scan7.2数据库预测调控靶基因的miRNAs。结果共筛选出630个DEGs(305个上调基因及325个下调基因),富集分析结果提示DEGs主要参与细胞外基质组织形成、蛋白质细胞外基质、肝素结合、化学致癌信号通路。进一步构建PPI网络,利用Cytoscape7.2数据库进行可视化分析,最终确定3个关键DEGs,包括VCAN、IGFBP7、FSTL1。利用GEPIA数据库验证关键DEGs,结果证实VCAN在胃癌组织中高表达(P<0.05),并与胃癌患者的不良预后有关。Target Scan7.2数据库预测结果提示has-miR-203a-3p.1可与VCAN mRNA的3′UTR结合。结论has-miR-203a-3p.1调控的VCAN是胃癌潜在治疗靶点。

Objective The bioinformatics approach was adapted to explore the mechanism of gastric caninogenesis and progression.Methods The differentially expressed genes(DEGs)between gastric cancer and normal gastric mucosa were identified by the GEO online tool from the microarray dataset GSE54129.The enrichment analyses of DEGs were conducted in the DAVID database.After the protein-protein interaction(PPI)network was constructed by STRING online database,the visualization was performed on Cytoscape software.The hub genes was identified both through MCODE and cytoHubba,which were validated by the GEPIA database and gastric cancer tissue samples.And then the miRNAs regulating target genes were predicted by the Target Scan 7.2 database.Results In total,there were 630 DEGs including 305 upregulated genes and 325 downregulated genes.Function enrichment analysis indicated that these DEGs were mainly involved in extracellular matrix organization,proteinaceous extracellular matrix,heparin binding,chemical carcinogenesis signal pathway.Through analysis of data from the PPI network,three hub genes were certificated by Cytoscape software including VCAN,IGFBP7,FSTL1.The results from the GEPIA database showed that VCAN expressed highly in gastric cancer tissues(P<0.05)and associated with poor prognosis of patients with gastric cancer.The prediction found that has-miR-203a-3p.1 might play a crucial role in VCAN regulation through binding 3′UTR of VCAN mRNA on the Target Scan7.2 database.Conclusion VCAN regulated by has-miR-230a-3p.1 is a potential target of therapy for gastric cancer.