骨关节炎患者滑膜组织miRNA-mRNA相互调控网络及分子作用机制的研究

Study on the miRNA-mRNA mutual regulation network and molecular mechanism of synovial tissue in patients with osteoarthritis

目的通过生物信息学分析明确骨关节炎患者滑膜组织内miRNA-mRNA调控网络及分子机制。方法miRNA和mRNA数据均来源于基因表达数据库(gene expression omnibus,GEO),利用R 4.0.3筛选出差异表达的miRNA和mRNA,通过GO富集分析明确差异基因主要富集的细胞组分、生物学进程以及分子功能,KEGG富集通路分析明确差异基因主要富集的信号通路。通过FunRich 3.1.3对差异表达的miRNA进行靶基因预测,预测靶基因与差异表达mRNA进行Venn图绘制获取共同差异基因,基于miRNA和共同差异基因构建miRNA-mRNA调控网络。结果GSE55457通过基因芯片技术检测健康患者滑膜以及骨关节炎患者滑膜的基因表达,GSE126677通过RNA测序技术检测健康患者滑膜以及骨关节炎患者滑膜的miRNA表达。最终通过数据分析共获得113个显著下调的差异表达mRNA、761个显著上调的差异表达mRNA;9个显著上调的差异表达miRNA、62个显著下调的差异表达miRNA。功能富集分析显示差异表达的mRNA参与细胞组分、生物学进程以及分子功能的功能调控;KEGG富集通路分析显示差异表达的mRNA主要参与整合素的调控、细胞生长因子的调控等多个信号通路。通过FunRich 3.1.3获得差异表达miRNA的预测靶基因并与本研究中差异表达的mRNA取交集后共获得9个差异表达的miRNA以及19个对应的mRNA,基于miRNA与mRNA之间的相互调控关系成功构建miRNA-RNA的调控网络。结论通过构建骨关节炎患者滑膜组织的miRNA-mRNA的相互调控网络,初步明确了骨关节炎患者滑膜组织病理变化的具体分子机制,为后续骨关节炎的诊断、治疗提供潜在的分子靶点。

Objective To clarify the miRNA-mRNA regulatory network and molecular mechanism in the synovial tissue of patients with osteoarthritis through bioinformatics analysis.Methods The miRNA and mRNA data were all from the Gene Expression Database(GEO).The differentially expressed miRNA and mRNA were screened using R 4.0.3,and the main enriched cell components,biological processes and biological processes of the differential genes were identified through GO enrichment analysis.KEGG enrichment pathway analysis clarified the main enrichment signal pathways of differential genes.Use FunRich 3.1.3 to predict differentially expressed miRNAs for target genes.Predict target genes and differentially expressed mRNAs to draw a Venn diagram to obtain common differential genes,and build miRNA-mRNA regulatory networks based on miRNAs and common differential genes.Results GSE55457 used gene chip technology to detect gene expression in the synovium of healthy participants and osteoarthritis patients,and GSE126677 used RNA sequencing technology to detect the expression of miRNA in the synovium of healthy participants and osteoarthritis patients.Finally,a total of 113 significantly down-regulated differentially expressed mRNAs and 761 significantly up-regulated differentially expressed mRNAs were obtained through data analysis;9 significantly up-regulated differentially expressed miRNAs and 62 significantlydown-regulated differentially expressed miRNAs.Functional enrichment analysis showed that differentially expressed mRNAs were involved in the functional regulation of cell components,biological processes and molecular functions;KEGG enrichment pathway analysis showed that differentially expressed mRNAs were mainly involved in the regulation of integrins and cell growth factors and other signals path.Obtain the predicted target genes of differentially expressed miRNAs through FunRich 3.1.3 and take the intersection with the differentially expressed mRNAs in this study to obtain a total of 9 differentially expressed miRNAs and 19 corresponding mRNAs.miRNA-RNA regulatory network was successfully constructed based on the mutual regulatory relationship between miRNAs and mRNAs.Conclusions By constructing the miRNA-mRNA mutual regulation network of the synovial tissue of patients with osteoarthritis,the specific molecular mechanism of the pathological changes of the synovial tissue of patients with osteoarthritis is preliminarily clarified,providing potential molecular targets for the subsequent diagnosis and treatment of osteoarthritis.