基于GEO数据库芯片探索miRNA参与肝纤维化的潜在机制

摘要/Abstract

摘要： 目的探讨生物信息学分析miRNA参与肝纤维化的潜在机制。方法通过GEO数据库获取小鼠肝纤维化miRNA芯片GSE19865及GSE66278数据,利用数据库软件GEO2R筛选差异miRNA。取两组芯片中同时上调的miRNA为研究目标,通过在线工具TargetScan及microT-CDS分析靶基因,取同时被两款软件预测到的基因进行功能分析。结果 GEO2R分析显示GSE19865芯片中miRNA上调37个,下调0个;GSE66278芯片中miRNA上调19个,下调18个;两组芯片中表达均上调的miRNA为mmu-miR-802。TargetScan及microT-CDS同时预测到的靶基因共有138个。通路分析显示这些靶基因主要参与线粒体生成,TGF-beta信号通路,组蛋白赖氨酸甲基化,Toll样受体信号传导等;生物学过程分析提示靶基因主要参与组蛋白赖氨酸甲基化,碱基转运,Wnt及钙调通路,JUN 激酶活化,基因表达的昼夜调控,葡萄糖饥饿的细胞应答, 蛋白类泛素化修饰,脂肪组织发育及细胞对氨基酸刺激的应答等。蛋白相互作用分析显示YWHAE、PPP2CA、RHOA、FOS、PSMD2、CDK19、ATF2、PAFAH1B1为调控网络中的关键基因。结论 miR-802参与肝纤维化的发生,其机制可能与miR-802靶向YWHAE、PPP2CA、RHOA等基因进而调控组蛋白甲基化等生物学过程相关。

关键词: 肝纤维化, 微小RNA, 生物信息学

Abstract: Objective To reveal the potential role of micro-ribonucleic acid (microRNA) in the pathogenesis of liver fibrosis.Methods MicroRNA microarray GSE19865 and GSE66278 were downloaded from gene expression omnibus (GEO) database. The data was analyzed with GEO2R. The microRNAs up-regulated in both microarrays were analyzed by TargetScan and microT-CDS for target gene prediction, and target genes predicted by both were further subjected to functional analysis. Results In GSE19865, 37 microRNAs were up-regulated, and none was down-regulated. While in GSE66278, 19 microRNAs were up-regulated and 18 microRNAs were down-regulated. The miR-802 was upregulated both in GSE19865 and GSE66278. A total of 138 candidate target genes were predicted by both TargetScan and microT-CDS. Functional analysis revealed that mainly function of these genes were participated in pathways and biological processes like mitochondrial biogenesis, transforming growth factor-beta signaling pathway, histone lysine methylation, Wnt/Ca²⁺ pathway, etc. Protein-protein interaction analysis identified YWHAE, PPP2CA, RHOA, FOS, PSMD2, CDK19, ATF2 and PAFAH1B1 as hub genes.Conclusion By integrated bioinformatics analysis, miR-802 is involved in the liver fibrosis. Mechanistically, miR-802 regulates biological processes including histone methylation by targeting genes like YWHAE, PPP2CA and RHOA.

Key words: Liver fibrosis, microRNA, Bioinformatics

黄翀, 郑雅慧, 张巨波. 基于GEO数据库芯片探索miRNA参与肝纤维化的潜在机制[J]. 肝脏, 2019, 24(12): 1381-1386.

HUANG Chong, ZHENG Ya-hui, ZHANG Ju-bo. Revealing role of miRNA in the pathogenesis of liver fibrosis by integrated bioinformatics analysis[J]. Chinese Hepatolgy, 2019, 24(12): 1381-1386.

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