基于生物信息学探讨骨关节炎miRNA-mRNA调控网络及其作用机制

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摘要目的: 基于生物信息学探讨骨关节炎miRNAmRMA调控网络的作用机制并筛选Hub基因，分析其在骨关节炎中的分子调控机制。方法: 通过GEO数据库获取骨关节炎的miRNA芯片数据集(GSE105027)和mRNA芯片数据集(GSE55235)，分析两者的差异表达基因。利用FunRich软件预测差异表达miRNAs的转录因子、功能富集分析及其靶基因预测，再将预测的靶基因与差异表达mRNAs进行交叉匹配，获得miRNAmRNA调控网络。然后利用STRING数据库和Cytoscape软件构建蛋白互作网络，并筛选出Hub基因。最后利用R语言分析Hub基因的主要生物功能与相关信号通路。结果: ① 筛选得到265个miRNAs和838个mRNAs存在差异表达。② 对265个miRNAs进行预测共得到203个转录因子，其中早期生长反应因子1（EGR1）差异最显著。富集分析显示miRNAs主要涉及核碱基、核苷、核苷酸和核酸代谢的调控，调节细胞生长，转录等过程。③ 共预测到3 572个靶基因，依据miRNA和mRNA的负调节关系，筛选出交叉表达负调控的mRNAs 96个、miRNAs 25个。④ 原癌基因Jun(JUN)、原癌基因Fos（FOS）、白介素6（IL-6）、肿瘤坏死因子（TNF）、白介素1β（IL-1β）、趋化因子CXCL8（CXCL8）为蛋白互作网络中的Hub基因。⑤ 富集分析主要涵盖对脂多糖的反应、对细菌来源分子的反应、DNA结合转录因子活性的调节等生物学过程，涉及IL-17、Toll样受体、AGERAGE、TNF和NOD样受体信号通路。结论: 成功筛选并构建了骨关节炎的miRNA-mRNA调控网络，在一定程度上阐明了miRNA及其靶基因在骨关节炎发生和发展中的分子调控机制。

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关键词 ：骨关节炎, 微小RNA, 调控网络, 生物信息学, GEO数据库

Abstract：［Abstract］Objective: Based on bioinformatics, the aim of this study is to explore the mechanism of osteoarthritis miRNAmRNA regulatory network, the Hub genes would be screened and its molecular regulatory mechanism in osteoarthritis is also analysed. Methods: Through the GEO database, the miRNA microarray dataset （GSE105027) and the mRNA microarray dataset （GSE55235) of osteoarthritis were obtained, and the differentially expressed genes were analyzed. Then FunRich software was used to predict the transcription factors of differentially expressed miRNAs, functional enrichment analysis and target gene prediction, and then the predicted target genes were crossed with the differentially expressed mRNAs to obtain the miRNAmRNA regulatory network. Then the STRING database and Cytoscape software were used to construct a protein interaction network and screen out the Hub genes. Finally, R language was used to analyze the function and related pathways of Hub gene. Results: ① A total of 265 miRNAs and 838 mRNAs were shown differentially expressed; ② The prediction of 265 miRNAs resulted in a total of 203 transcription factors, of which EGR1 had the most significant difference. Enrichment analysis showed that miRNAs were mainly involved in the regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism, cell growth regulation, transcription and other processes; ③ A total of 3 572 target genes were predicted, and the screening was based on the negative regulatory relationship between miRNA and mRNA. And 96 mRNAs and 25 miRNAs with negative regulation of cross-expression were identified; ④ JUN, FOS, IL-6, TNF, IL-1β, and CXCL8 are the Hub genes in the protein interaction network; ⑤ The enrichment analysis mainly covers biological processes such as the response to lipopolysaccharide, the response to bacteria-derived molecules, and the regulation of DNAbinding transcription factor activity, involving IL-17, Toll-like receptors, AGERAGE, TNF and NODlike receptors signaling pathways. Conclusion: The miRNAmRNA regulatory network of osteoarthritis was successfully screened and constructed, and the molecular regulation mechanism of miRNA and its target genes in the occurrence and development of osteoarthritis was clarified to a certain extent.

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收稿日期: 2021-12-17

基金资助:［基金项目］广西自然科学基金青年基金（2020GXNSFBA159053）；广西壮族自治区临床重点专科(创伤外科)建设项目［部门预算社(2021)］；广西壮族自治区卫生厅自筹经费科研课题（Z2013246）；广西中医药大学2021年校级科研课题（XYJ21156

通讯作者: 陈涛（通讯作者），副主任医师，E-mail：chentaoky@163.com

作者简介: ［作者简介］陈锋（1996—），男，硕士研究生；

引用本文:

陈锋，陈涛，章晓云，等.. 基于生物信息学探讨骨关节炎miRNA-mRNA调控网络及其作用机制[J]. 江苏大学学报:医学版, 2022, 32(05): 391-397,402. CHEN Feng, CHEN Tao, ZHANG Xiaoyun, CHEN Yueping, CHAI Yuan. Bioinformatics exploration on the mechanism of osteoarthritis miRNA-mRNA regulatory network. Journal of Jiangsu University(Medicine Edition), 2022, 32(05): 391-397,402.

链接本文:

http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2022/V32/I05/391

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