整合分析肝细胞癌DNA甲基化谱和基因表达谱构建miR-1180-3p相关ceRNA调控网络

Integrated analysis of DNA methylation and gene expression profiles of hepatocellular carcinoma to construct miR-1180-3p relevant ceRNA regulatory network

目的通过整合癌症基因组图谱中肝细胞癌DNA甲基化谱和基因表达谱,分析肝细胞癌中miR-1180-3p表达水平并构建其相关ceRNA调控网络。方法用癌症基因组图谱数据库分析肝细胞癌及癌旁组织中miR-1180-3p的表达水平,并筛选出差异表达长链非编码RNA(lncRNA)和mRNA。分别用LncBase数据库和TargetScan数据库预测miR-1180-3p与lncRNA和mRNA的靶向作用关系,并通过lncRNA的DNA甲基化谱筛选出DNA甲基化介导的lncRNA。用Cytoscape软件构建miR-1180-3p相关ceRNA网络,并用WebGestalt网站对ceRNA中相关mRNA进行GO分析和KEGG分析。结果相比于低表达miR-1180-3p的患者[总生存时间(5.69±0.35)年],高表达miR-1180-3p患者的总生存时间较短[总生存时间(3.99±0.47)年],提示miR-1180-3p高表达是影响肝细胞癌预后的危险因素(风险比=1.28,95%可信区间为1.1~1.5,P<0.01)。研究中构建的miR-1180-3p相关ceRNA调控网络包含2个lncRNA(F11-AS1和LINC01511)以及37个mRNA。结论成功构建了miR-1180-3p相关ceRNA调控网络,其中DNA甲基化介导的F11-AS1及F11-AS1/miR-1180-3p/C11of54 ceRNA调控轴在肝细胞癌的发生和发展中起重要作用。

Objective This study analyzes the expression level of miR-1180-3p and constructs the regulatory network of relevant ceRNA by integrating the DNA methylation and gene expression profile of hepatocellular carcinoma from the Cancer Genome Atlas(TCGA).Methods Firstly,the expression level of miR-1180-3p in hepatocellular carcinoma and adjacent tissues was analyzed by TCGA database,and the differential expression of lncrna and mRNA was screened.Secondly,the LncBase database and the TargetScan database were used to predict the relationship between miR-1180-3p and lncRNA and mRNA,and the DNA methylation-mediated lncRNA was screened by the DNA methylation profile of lncRNA.Finally,Cytoscape software was used to construct miR-1180-3p relevant ceRNA network,and WebGestalt website was used to perform GO and KEGG analysis of related mRNA in ceRNA.Results Compared with patients with low expression of miR-1180-3p(mean overall survival duration,5.69±0.35 years),patients with high expression of miR-1180-3p had shorter overall survival time(mean overall survival duration,3.99±0.47 years),indicating that the high expression of miR-1180-3p was hepatocellular carcinoma risk factor affecting the prognosis(HR=1.28,95%CI=1.1~1.5,P<0.01).A miR-1180-3p related ceRNA regulatory network was constructed in this study,which contained 2 lncRNAs(F11-AS1 and LINC01511)and 37 mRNAs.Conclusion This study has successfully constructed miR-1180-3p relevant ceRNA regulatory network,and DNA methylation-mediated F11-AS1 and F11-AS1/miR-1180-3p/C11of54 ceRNA regulatory axis has played an important role in the occurrence and development of hepatocellular carcinoma.