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肝细胞癌DNA甲基化与基因表达谱的综合分析以构建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].

作者信息

Zhou Z H, Zhou X G, Zhou Z W, Qiu M Q, Jiang Y J, Lin Q L, Liu Y C, Wen Q P, Huo R R, Liang X M, Yu H P

机构信息

Guangxi Medical University Cancer Hospital, Nanning 530021, China; School of Public Health, Guangxi Medical University, Nanning 530021, China.

Guangxi Medical University Cancer Hospital, Nanning 530021, China.

出版信息

Zhonghua Gan Zang Bing Za Zhi. 2020 Jun 20;28(6):481-487. doi: 10.3760/cma.j.cn501113-20200103-00003.

Abstract

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). 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. 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 ( = 1.28, 95% = 1.1 ~ 1.5, < 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. 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.

摘要

本研究通过整合癌症基因组图谱(TCGA)中肝细胞癌的DNA甲基化和基因表达谱,分析miR-1180-3p的表达水平并构建相关ceRNA的调控网络。首先,利用TCGA数据库分析miR-1180-3p在肝细胞癌及癌旁组织中的表达水平,并筛选lncrna和mRNA的差异表达。其次,使用LncBase数据库和TargetScan数据库预测miR-1180-3p与lncRNA和mRNA之间的关系,并通过lncRNA的DNA甲基化谱筛选DNA甲基化介导的lncRNA。最后,利用Cytoscape软件构建miR-1180-3p相关ceRNA网络,并使用WebGestalt网站对ceRNA中的相关mRNA进行GO和KEGG分析。与miR-1180-3p低表达患者(平均总生存时长,5.69±0.35年)相比,miR-1180-3p高表达患者的总生存时间较短(平均总生存时长,3.99±0.47年),表明miR-1180-3p高表达是影响肝细胞癌预后的危险因素(=1.28,95%=1.1~1.5,<0.01)。本研究构建了一个miR-1180-3p相关ceRNA调控网络,其中包含2个lncRNA(F11-AS1和LINC01511)和37个mRNA。本研究成功构建了miR-1180-3p相关ceRNA调控网络,DNA甲基化介导的F11-AS1以及F11-AS1/miR-1180-3p/C11of54 ceRNA调控轴在肝细胞癌的发生发展中发挥了重要作用。

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