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Bioinformatics Analysis Identified the Hub Genes, mRNA-miRNA-lncRNA Axis, and Signaling Pathways Involved in Rheumatoid Arthritis Pathogenesis.


ABSTRACT:

Objective

Rheumatoid arthritis (RA) is a nonspecific, chronic, systemic autoimmune disease characterized by symmetric polyarticular synovitis. Bioinformatics analysis of potential biomarkers, mRNA-miRNA-lncRNA axes, and signaling pathways in the pathogenesis of RA provides potential targets and theoretical basis for further research on RA.

Methods

The GSE1919 and GSE77298 datasets were downloaded from the Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo). Perl was used to perform data merging, and R was used to perform batch correction. The "limma" package of R was used to screen differentially expressed genes, and the "clusterProfiler" package was used to perform enrichment analysis of the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Search Tool for the Retrieval of Interacting Genes/Proteins was used to construct the protein-protein interaction network, Cytoscape was used for module analysis, and R was used to screen for hub genes. GraphPad Prism was used to plot the receiver operating characteristic curve of the hub genes. Gene set enrichment analysis and competitive endogenous RNA network analysis were performed on hub genes with the greatest diagnostic values. The hub gene with the greatest diagnostic value was verified using immunohistochemical staining.

Results

We obtained nine hub genes (ITGB2, VAMP8, HLA-A, PTAFR, SYK, FCER1G, HLA-DPB1, LCP2, and ACTR2) and four mRNA-miRNA-lncRNA axes (ITGB2-hsa-miR-486-3p-SNHG3, ITGB2-hsa-miR-338-5p-XIST, ITGB2-hsa-miR-5581-3p-XIST, and ITGB2-hsa-miR-1226-5p-XIST) related to the pathogenesis of RA. The nine hub genes were highly expressed, and ITGB2 had the highest diagnostic value for RA. We also identified signaling pathways related to the pathogenesis of RA: Fc epsilon Rl and chemokine signaling pathways. The immunohistochemical results showed that ITGB2 expression was significantly upregulated in RA.

Conclusion

The hub genes, mRNA-miRNA-lncRNA axes, and signaling pathways related to RA pathogenesis identified in this study provide a new research direction for the mechanism, diagnosis, and treatment of RA.

SUBMITTER: Yang M 

PROVIDER: S-EPMC9005080 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Bioinformatics Analysis Identified the Hub Genes, mRNA-miRNA-lncRNA Axis, and Signaling Pathways Involved in Rheumatoid Arthritis Pathogenesis.

Yang Mingyi M   Zheng Haishi H   Su Yani Y   Xu Ke K   Yuan Qiling Q   Aihaiti Yirixiati Y   Cai Yongsong Y   Xu Peng P  

International journal of general medicine 20220408


<h4>Objective</h4>Rheumatoid arthritis (RA) is a nonspecific, chronic, systemic autoimmune disease characterized by symmetric polyarticular synovitis. Bioinformatics analysis of potential biomarkers, mRNA-miRNA-lncRNA axes, and signaling pathways in the pathogenesis of RA provides potential targets and theoretical basis for further research on RA.<h4>Methods</h4>The GSE1919 and GSE77298 datasets were downloaded from the Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo). Perl was  ...[more]

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