Journal
FRONTIERS IN IMMUNOLOGY
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.881191
Keywords
DNA methylation; rheumatoid arthritis; miRNA; m6A methylation; epigenetic regulation; gene expression
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Funding
- National Key Technologies R&D ProgramofChina
- Ministry of Science and Technology of the People's Republic of China [2019YFC0840701]
- CAMS Innovation Fund for Medical Sciences [2019-I2M-5-027]
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This study comprehensively analyzed the epigenetic regulation in rheumatoid arthritis (RA) using differential analysis and cross-analysis. The results identified differentially methylated sites, differentially expressed genes, and differentially expressed miRNAs associated with RA. A comprehensive epigenetic regulatory network was constructed, and core regulatory genes were identified. This study provides a new direction for future research on the epigenetic mechanisms of RA.
PurposeRheumatoid arthritis (RA) is a disease associated with multiple factors. Epigenetics can affect gene expression without altering the DNA sequence. In this study, we aimed to comprehensively analyze epigenetic regulation in RA. MethodsUsing the Gene Expression Omnibus database, we identified a methylation chip, RNA-sequencing, and miRNA microarray for RA. First, we searched for DNA methylation, genes, and miRNAs associated with RA using differential analysis. Second, we determined the regulatory networks for RA-specific methylation, miRNA, and m6A using cross-analysis. Based on these three regulatory networks, we built a comprehensive epigenetic regulatory network and identified hub genes. ResultsUsing a differential analysis, we identified 16,852 differentially methylated sites, 4877 differentially expressed genes, and 32 differentially expressed miRNAs. The methylation-expression regulatory network was mainly associated with the PI3K-Akt and T-cell receptor signaling pathways. The miRNA expression regulatory network was mainly related to the MAPK and chemokine signaling pathways. M6A regulatory network was mainly associated with the MAPK signaling pathway. Additionally, five hub genes were identified in the epigenetic regulatory network: CHD3, SETD1B, FBXL19, SMARCA4, and SETD1A. Functional analysis revealed that these five genes were associated with immune cells and inflammatory responses. ConclusionWe constructed a comprehensive epigenetic network associated with RA and identified core regulatory genes. This study provides a new direction for future research on the epigenetic mechanisms of RA.
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