Preprint Review Version 2 Preserved in Portico This version is not peer-reviewed

Epigenetic Regulation Mediated by microRNAs 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 microRNAs in the Susceptibility and Pathogenesis of Rheumatoid Arthritis. Preprints 2020, 2020040241 (doi: 10.20944/preprints202004.0241.v2). Guo, S.; Chang, C.; Xu, L.; Zhang, R.; Jin, Y.; Xiong, M.; He, D. Epigenetic Regulation Mediated by microRNAs in the Susceptibility and Pathogenesis of Rheumatoid Arthritis. Preprints 2020, 2020040241 (doi: 10.20944/preprints202004.0241.v2).

Abstract

MicroRNAs (miRNAs) play crucial roles in the regulation of the transcriptome and development of diseases including cancer and autoimmune diseases, such as rheumatoid arthritis (RA). Currently, a comprehensive map, illustrating how miRNAs regulate transcripts, pathways, immune system differentiation, and their interaction with terminal cells, such as T cells, fibroblast-like synoviocytes (FLS), osteoblasts, and osteoclasts, is still missing. In this review, we provide a thorough summary of the roles of miRNAs in the susceptibility to pathogenesis, diagnosis, therapeutic intervention, and prognosis of RA. Numerous miRNAs are abnormally expressed in cells involved in RA, and regulate target genes and pathways including the NF-κB, Fas-FasL, JAK-STAT, IRE1-RIDD, and mTOR pathways. By regulating gene expression, miRNAs affect T cell differentiation to diverse cell types, including Th17 and T-reg cells, and thus constitute promising gene therapy targets to modulate the immune system in RA. We summarize the diagnostic and prognostic potential of blood-circulating and cell-free miRNAs, highlighting the novel opportunities to combine these with rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) to provide accurate diagnosis and prognosis, especially for seronegative patients. Furthermore, we outline how functional genetic variants of miR-499 and miR-146a partly explain the unmet susceptibility to RA. Additionally, we review the evidence implicating miRNAs as promising biomarkers of efficiency, response, and resistance to disease-modifying anti-rheumatic drugs (DMRDs) and immunotherapy. Finally, we discuss the autotherapeutic effect of miRNA intervention as a step toward the development of miRNA-based anti-RA drugs. Collectively, the current evidence supports miRNAs as interesting targets to better understand the pathogenetic mechanisms of RA and design more efficient therapeutic interventions.

Subject Areas

rheumatoid arthritis; miRNA; susceptibility; pathogenesis; epigenetics

Comments (1)

Comment 1
Received: 22 April 2020
Commenter: Cen Chang
Commenter's Conflict of Interests: Author
Comment: change the figure and some details of the article
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