程晓平,郑文伟,倪国新.基于微小核糖核酸-信使核糖核酸调控网络的骨关节炎病变的相关分子机制研究[J].中华物理医学与康复杂志,2022,44(4):306-311
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| 基于微小核糖核酸-信使核糖核酸调控网络的骨关节炎病变的相关分子机制研究 |
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| DOI：10.3760/cma.j.issn.0254-1424.2022.04.004 |
| 中文关键词: 骨关节炎 微小核糖核酸 信使核糖核酸 调控网络 |
| 英文关键词: Osteoarthritis Micro-RNA mRNA Regulatory networks |
| 基金项目: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） |
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| 中文摘要: |
| 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。 |
| 英文摘要: |
| 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. |
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