Construction Of CeRNA Regulatory Network In Rheumatoid Arthritis And Its Correlation With Immune Cells

Objective:In this study,bioinformatics methods were used to construct the regulatory network of competing endogenousRNA（ceRNA）in synovial tissues of RA patients and to analyze the infiltration of immune cells.The pathogenesis of the disease was also discussed.Methods:（1）The Gene Expression Omnibus（GEO）database was used to detect messengerRNA（mRNA）and long non-codingRNA（LONG non-codingRNA）in synovial tissues of RA patients.Differentially expressed mRNAs（DEmRNAs）and differentially expressed lncRNAs（DElncRNAs）were obtained by differential analysis.（2）Target miRNA and target mRNA related to RA were obtained through miRNA databases,and then lncRNA-miRNA-mRNA ceRNA regulation network was constructed.（3）Gene Ontology（GO）and Kyoto Genomic Encyclopedia（KEGG）pathway enrichment analysis was performed for differentially expressed mRNAs,（DEmRNAs）in the ceRNA regulation network and core DEmRNAs were screened.（4）The content and proportion of 22 types of immune cells in RA synovial tissue and control group were analyzed by CIBERSORT.Results:（1）The object of study: 61 RA cases and 46 health control samples were obtained from Gene Expression Omnibus（GEO）database.（2）CeRNA network construction: The lncRNA-miRNA-mRNA regulatory network was constructed,and the results showed that the network included 38 miRNA nodes,18 lncRNA nodes and 228 mRNA nodes.（3）Pathway enrichment analysis showed that the up-regulated DEmRNAs enrichment pathway were mitogen-activated protein kinase（MAPK）signaling pathway,and rat sarcoma virus（RAS）,Epidermal growth factor receptor（ERBB）signaling pathway was the main enrichment pathway of down-regulated genes,and 10 core genes DEmRNAs（MYC,JUN,EZH2,FOXO3,PPARG,FOS,VEGFA,NRAS,FOXO1,CDKN1A）were screened out.（4）CIBERSORT results showed that 13 types of immune cells were differentially expressed in RA patients and controls,and the core genes CDKN1 A,MYC,JUN,VEGFA and FOS were correlated with the number of some immune cells.Conclusions: In this study,through the construction of ceRNA regulatory network,it was found that the main DEmRNAs enrichment signaling pathway in the network,and combined with the comprehensive analysis of immune cell infiltration in the synovial tissue of RA patients,providing a new idea for further exploring the pathogenesis of RA.