酒精性肝炎microRNA-mRNA差异表达网络的生物信息学分析

张秀芝; 李宁宁; 刘晓丽; 亢春彦; 张进忠

doi:10.3969/j.issn.1001-5256.2019.03.026

酒精性肝炎microRNA-mRNA差异表达网络的生物信息学分析

DOI: 10.3969/j.issn.1001-5256.2019.03.026

1. 河南医学高等专科学校病理教研室
2. 河南省人民医院检验科

基金项目:

河南省科技攻关计划项目(142102310441)；

详细信息

中图分类号: R575.1
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出版历程
- 出版日期: 2019-03-20

A bioinformatics analysis of the microRNA-mRNA differential expression network for alcoholic hepatitis

Department of Pathology, Henan Medical College

Research funding:

摘要

摘要:
目的构建酒精性肝炎（AH）的microRNA-mRNA差异表达网络,寻找AH新的诊疗靶标。方法筛选AH差异表达的microRNA和mRNA;基于TargetScan、DIANA、MIRDB、PICTAR、miRWalk2. 0等软件寻找差异microRNA靶基因,选取差异mRNA中与microRNA变化方向相反的靶基因,构建关键microRNA-mRNA网络;通过注释、可视化和集成发现数据库（DAVID）对相关靶基因进行基因本体论（GO）分析、京都基因与基因组百科全书数据库（KEGG）通路分析;通过GCBI （www. gcbi. com. cn）在线软件对靶基因进行疾病富集分析和核心网络构建;通过Cytoscape软件中GeneMANIA数据库（genemania. org）对关键靶基因进行蛋白相互作用分析,对比3种方法通路分析寻找AH发生过程中的关键通路。结果构建以hsa-mir-21-5p、hsa-mir-148a-3p和hsa-mir-30e-5p等5个差异microRNA及Ⅳ胶原α1链（COL4A1）、血栓反应素2（THBS2）和整合素亚单位α6（ITGA6）等51个靶基因为...
- 肝炎,酒精性 /
- 微RNA /
- RNA,信使 /
- 基因调控网络 /
- 信号传导 /
- 基因疗法
Abstract:
Objective To establish a microRNA-mRNA differential expression network for alcoholic hepatitis ( AH) , and to investigatenew targets for the diagnosis and treatment of AH. Methods Differentially expressed microRNAs and mRNAs between AH patients and nor-mal controls were screened out. Related software including TargetScan, DIANA, MIRDB, PICTAR, and miRWalk 2. 0 was used to searchfor the target genes of differentially expressed microRNA, and a key microRNA-mRNA network was established using the differentially ex-pressed mRNAs that changed in an opposite way to microRNA. The Database for Annotation, Visualization and Integrated Discovery wasused for the gene ontology ( GO) and Kyoto Encyclopedia of Genes and Genome ( KEGG) analyses of target genes. The GCBI online soft-ware ( www. gcbi. com. cn) was used for enrichment analysis of target genes and core network establishment. The GeneMANIA database inCytoscape software ( genemania. org) was used to perform a protein-protein interaction analysis of key target genes. The above three meth-ods were compared in terms of the search for key pathways involved in the development of AH. Results A key microRNA-mRNA networkwas established with 5 differentially expressed microRNAs including hsa-mir-21-5 p, hsa-mir-148 a-3 p, and hsa-mir-30 e-5 pand 51 target genes including collagen type IV alpha 1 chain ( COL4 A1) , thrombospondin-2 ( THBS2) , and integrin alpha 6 ( IGTA6) . Aprotein-protein interaction network of key target genes was established. The GO analysis and various pathway analyses showed that the PI3 K-Akt pathway and local adhesion were closely associated with AH. Conclusion During the development of AH, there are complex interac-tions between the related proteins of key target genes. COL4 A1 and THBS2 may promote the development of AH by activating ITGA6 to regu-late the PI3 K-Akt pathway and the process of local adhesion. The establishment of the microRNA-mRNA network reveals the key links inthe development of AH and highlights the focus of research. The discovery of the genes associated with the PI3 K-Akt pathway in AH is ex-pected to provide new targets for the diagnosis and treatment of AH.
- hepatitis, alcoholic /
- microRNAs /
- RNA, messenger /
- gene regulatory networks /
- signal transduction /
- gene therapy

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