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| Construction of lncRNA-miRNA-mRNA network and prediction of key genes in rheumatoid arthritis fibroblast-like synoviocytes |
| ZHOU Xinpeng1,2 JIN Yehua1,2 ZHANG Runrun1,2 HE Dongyi1,2 |
1.Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China;
2.Department of Arthrology, Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200052, China |
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Abstract Objective To explore the long non-coding RNA (lncRNA) -microRNA (miRNA) -mRNA network and key lncRNA in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS), and to reveal the role of lncRNA in RA. Methods Data sets GSE103578, GSE83147 and GSE128813 were obtained from Gene Expression Omnibus (GEO) of the National Center for Biotechnology Information in the United States. Each data set contained three synovium-isolated FLS from healthy people in the control group and three FLS from RA patients in the RA group. R language program, idmap3 package was used for probe annotation. Limma package was used to standardize the data, remove batch effect and analyze gene differential expression. LogFC > 1.0 and P < 0.05 were used as the criteria for differential expression. Correlation analysis was conducted for the differentially expressed lncRNA and mRNA. In the lncbase, starBase and miRcode databases, the miRNAs related to lncRNA were obtained, and the miRNAs related to mRNA were searched in the miRWalk and TargetScan databases. The intersection of the two was taken, and the lncRNA-miRNA-mRNA network was constructed by Cytoscape software, and the lncRNAs in the network were taken as the key lncRNA. Results After standardization of GEO data set, elimination of batch effect and annotation, 14 760 mRNAs and 5290 lncRNAs were finally obtained. Compared with the control group, there were 31 mRNA up-regulated and 56 mRNA down-regulated in RA group, and 9 up-regulated genes and 14 down-regulated genes in lncRNA. The Pearson correlation coefficient R > 0.85 and P < 0.05 were used as the criteria for the co-expression of lncRNA-mRNA genes, and 18 co-expressed lncRNAs and 51 mRNAs were obtained. There were 26 miRNAs that had binding sites with co-expressed lncRNA and mRNA. In the constructed lncRNA-miRNA-mRNA co-expression network, there were 13 lncRNAs, including lncRNA XIST, NR2F2-AS1, LINC01018, etc., 26 miRNAs and 46 mRNAs. Conclusion Thirteen lncRNAs, such as lncRNA XIST, NR2F2-AS1, LINC01018, are differentially expressed in RA-FLS, and the expression of miRNA and mRNA is regulated through the competitive endogenous RNA mechanism to form a regulatory network of lncRNA-miRNA-mRNA, which could be used as the target lncRNA for further verification.
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