摘要
目的基于生物信息学方法构建类风湿性关节炎核心微小RNA(miRNA)-mRNA调控网络并筛选相关核心基因,探索其在类风湿性关节炎疾病中的分子调控机制。方法从基因表达综合(GEO)数据库下载miRNA和mRNA基因表达谱芯片GSE72564和GSE55235。采用GEO2R分析工具筛选差异表达的miRNA和mRNA,应用miRNet在线数据库分析预测miRNA差异表达的靶基因并与mRNA数据集筛选出的差异基因进行交叉匹配,获得miRNA-mRNA相互作用关系对。使用ClusterProfiler包对miRNA-mRNA的差异基因进行基因本体论(GO)富集分析和京都基因与基因组百科全书(KEGG)富集分析。应用Cytoscape软件绘制miRNA-mRNA调控网络图并使用cytohubba插件进行Hub基因分析。结果共筛选出差异miRNA23个,筛选到差异基因1038个。交叉匹配后获得142个差异基因,GO分析发现其主要与缺氧反应及细胞黏附分子结合等生物过程和分子功能相关。KEGG分析表明其主要参与调控磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/AKT)、Th17细胞分化、Th1/Th2细胞分化等信号通路。成功构建miRNA-mRNA调控网络,筛选出8个DE-miRNA,其中hsa-miR-218-5p属于高频下调表达的miRNA,可靶向作用于KLHL21和HSPG2。结论基于数据挖掘和芯片分析技术成功构建类风湿性关节炎miRNA-mRNA调控网络,有助于阐明miRNA及其靶基因在类风湿性关节炎发生和发展中的分子调控机制,为类风湿性关节炎的靶向诊断和治疗提供可靠的理论基础。
Objective To construct the core miRNA-mRNA regulatory network of rheumatoid arthritis based on bioinformatics methods and screen related core genes to explore its molecular regulatory mechanism in rheumatoid arthritis disease.Methods Download miRNA and mRNA gene expression profiling chips GSE72564 and GSE55235 from GEO database.The GEO2R analysis tool was used to screen differentially expressed miRNA and mRNA,and the miRNet online database was used to analyze and predict the differentially expressed target genes of miRNA and cross-match with the differential genes selected from the mRNA data set to obtain miRNA-mRNA interaction relationship pairs.The differential genes of miRNA-mRNA were analyzed by GO and KEGG using ClusterProfiler.Cytoscape software was used to draw the miRNA-mRNA regulatory network and CytoHubba plug-in was used for hub gene analysis.Results A total of 23 differential miRNA were screened.A total of 1038 differential genes were screened.After cross-matching,142 differential genes were obtained.GO analysis found that they were mainly related to biological processes and molecular functions such as hypoxia response and cell adhesion molecules binding.KEGG analysis showed that it was mainly involved in the regulation of PI3K/AKT,Th17 cell differentiation,Th1/Th2 cell differentiation and other signaling pathways.The miRNA-mRNA regulatory network was successfully constructed and 8 DE-miRNAs were screened out.Among them,hsa-miR-218-5p was a high-frequency down-regulated miRNA,which can target KLHL21 and HSPG2.Conclusion The successful construction of rheumatoid arthritis miRNA-mRNA regulatory network based on data mining and chip analysis technology will help clarify the molecular regulatory mechanism of miRNA and its target genes in the occurrence and development of RA,and provide targeted diagnosis and treatment of RA Reliable theoretical basis.
作者
曹维维
袁成良
CAO Weiwei;YUAN Chengliang(Department of Clinical Laboratory,Deyang People′s Hospital,Deyang,Sichuan 618000,China)
出处
《国际检验医学杂志》
CAS
2021年第5期608-612,共5页
International Journal of Laboratory Medicine
基金
德阳市科技局项目(2017SZ019)。
