摘要
目的基于miRNA-mRNA调控网络进行生物信息学分析,探讨骨关节炎病变的相关分子机制。方法从GEO数据库下载人血清样本miRNA表达数据集,通过R语言limma包获取差异表达miRNA,采用miRwalk 2.0版数据库预测其对应靶基因(mRNA),并构建miRNA-mRNA调控网络。对靶基因进行功能GO分析和KEGG信号通路分析,构建靶基因所编码的蛋白质相互作用网络(PPI),从中筛选出骨关节炎病变的核心基因。结果共筛选出7个差异表达的miRNA(表达均为下调)和900个mRNA,这些基因主要涉及蛋白结合、DNA结合、转录等生理过程,参与Cell cycle、p53、Neurotrophin、PI3K-Akt等信号通路。蛋白相互作用分析表明MAPK1、TP53、MAPK14、CCND1、EP300、POLR2E、POLR2F、ABL1、RAC1、SKIV2L2为该调控网络的核心靶基因。结论OA的发生和发展涉及多个的miRNA、靶基因和作用途径,而通过构建骨关节炎相关miRNA-mRNA调控网络,可为找出骨关节炎病的分子机制和今后临床上诊疗提供新的思路。
Objective To explore the molecular mechanism of pathological changes in osteoarthritis(OA)through applying bioinformatics to analyze the miRNA-mRNA regulatory network.Methods MiRNA expression data from human serum samples were downloaded from the Gene Expression Omnibus database.Differentially-expressed miRNA was identified using the linear modelling package of the Bioconductor software suite.The target differentially-expressed mRNA was predicted using version 2.0 of the miRWalk database.Version 3.7.1 of the Cytoscape software was used to construct the miRNA-mRNA regulatory network for OA.The target genes were analyzed by using gene ontology and the Kyoto Encyclopedia of Genes and Genomes.The protein-protein interaction network was constructed and the core genes in osteoarthritis pathology were screened out.Results A total of 7 differentially-expressed miRNAs(all down-regulated)and 900 mRNAs were identified,mostly involved in the negative regulation of protein binding,DNA binding,or transcription in the cell cycle.Ten core genes were screened out:MAPK1,TP53,MAPK14,CCND1,EP300,POLR2E,POLR2F,ABL1,RAC1 and SKIV2L2.Conclusions Multiple miRNAs,target genes and signaling pathways are involved in the development of OA.The miRNA-mRNA regulatory network identified provides new ideas for exploring the molecular mechanism of OA′s pathology and its clinical diagnosis and treatment.
作者
程晓平
郑文伟
倪国新
Cheng Xiaoping;Zheng Wenwei;Ni Gaoxin(Department of Rehabilitation,The First Affiliated Hospital of Fujian Medical University,Fuzhou 350000,China;Fujian Institute of Microbiology,Fiuhoa 350000,China;Beijing Sport University,Beijing 100084,China)
出处
《中华物理医学与康复杂志》
CAS
CSCD
北大核心
2022年第4期306-311,共6页
Chinese Journal of Physical Medicine and Rehabilitation
基金
国家自然科学基金(81572219)
福建省卫生健康青年科研课题(2021QNA024)
福建医科大学启航基金项目(2020QH1017)。
