Preprint Review Version 1 This version is not peer-reviewed

Epigenetic Regulation Mediated by miRNA in the Susceptibility and Pathogenesis of Rheumatoid Arthritis

Version 1 : Received: 14 April 2020 / Approved: 15 April 2020 / Online: 15 April 2020 (10:03:47 CEST)
Version 2 : Received: 19 April 2020 / Approved: 22 April 2020 / Online: 22 April 2020 (05:52:20 CEST)

How to cite: Guo, S.; Chang, C.; Xu, L.; Zhang, R.; Jin, Y.; Xiong, M.; He, D. Epigenetic Regulation Mediated by miRNA in the Susceptibility and Pathogenesis of Rheumatoid Arthritis. Preprints 2020, 2020040241 (doi: 10.20944/preprints202004.0241.v1). Guo, S.; Chang, C.; Xu, L.; Zhang, R.; Jin, Y.; Xiong, M.; He, D. Epigenetic Regulation Mediated by miRNA in the Susceptibility and Pathogenesis of Rheumatoid Arthritis. Preprints 2020, 2020040241 (doi: 10.20944/preprints202004.0241.v1).

Abstract

micro-RNA (miRNA) has been demonstrated to play important roles in the transcriptome regulation and disease development including cancer and autoimmune disease such as rheumatoid arthritis. However, a comprehensive map on how the mRNAs regulate transcripts, pathways, immune system differentiation and interaction with terminal cells like T-cells, fibroblast-like synoviocytes (FLS), osteoblast and osteoclast still unknown. In this review, we have provided a thorough summary on the roles of miRNAs in the susceptibility, pathogenesis, diagnosis, therapeutic intervention and prognosis. Numerous miRNAs were found abnormally expressed in rheumatoid arthritis relevant cells and regulated the target genes and pathways like NF-κB, Fas-FasL, JAK-STAT, IRE1-RIDD, mTOR pathway. In addition, miRNA act as gene expression regulators affect the T-cell differentiate to different cell types including Th17 and T-reg cells which provide promising gene therapy target to regulate immune systems in rheumatoid arthritis. We also summarized interesting diagnosis and prognosis roles of blood and cell-free based miRNAs which provided novel opportunity to work together with rheumatoid factors (RF), anti-CCP to provide accurate diagnosis and prognosis especially for seronegative patients. Furthermore, functional genetic variants in miRNA-499 and miRNA-146a explained part of missing susceptibility of rheumatoid arthritis. Finally, miRNAs were showed as promising biomarker to indicate the DMRDS and immunotherapy efficiency, drug response and resistance. What’s more, autotherapeutic effect of miRNA intervention provided promising to develop miRNA based rheumatoid arthritis drugs. Overall, current evidence supports miRNAs as the interesting targets to better understand the pathogenetic mechanism and therapeutic intervention of rheumatoid arthritis.

Subject Areas

rheumatoid arthritis; miRNA; susceptibility; pathogenesis; Epigenetics

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