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

Abstract

Contribution: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 role of miRNAs in rheumatoid arthritis (RA) including immune system differentiation and interaction with terminal cells like T cells, fibroblast-like synoviocytes (FLS), osteoblast and osteoclast still unclear. In this review, we have provided a thorough summary on the roles of miRNAs in the susceptibility, pathogenesis, diagnosis, therapeutic intervention and prognosis. We summarized the blood and cell-free miRNA biomarkers which provided novel opportunity to work together with rheumatoid factors (RF), anti-CCP to provide accurate diagnosis and prognosis especially for seronegative patients. 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the pathogenetic mechanism and therapeutic intervention of rheumatoid arthritis.Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 15 April 2020 Abstract micro-RNA (miRNA) has been demonstrated to play important roles in the transcriptome regulation and disease development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 miR-499 and miR-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 inter...

Epigenetic Regulation Mediated by Methylation in the Pathogenesis and Precision Medicine of Rheumatoid Arthritis

“…RA-associated genetics thoroughly explain neither the heterogeneity of the clinical characteristics nor the treatment differences among patients with RA. In recent years, more and more studies have started to focus on the role of epigenetics in RA ( Ai et al, 2018 ; Guo et al, 2019 , 2020 ; Tseng et al, 2019a ) and investigate the contribution of epigenetics to the heterogeneity of RA. DNA methylation and histone modifications, important epigenetic modifications that affect the expression of immune-related genes and inflammation progression ( Meng et al, 2015 ; Lawrence et al, 2016 ) have become promising mechanisms to explain the pathogenesis of RA ( Mazzone et al, 2019 ).…”

Epigenetic Regulation Mediated by Methylation in the Pathogenesis and Precision Medicine of Rheumatoid Arthritis

“…In the recent years, more and more studies have focused on the role of epigenetics in RA(Ai et al, 2018;Guo et al, 2019;Tseng et al, 2019a;Guo et al, 2020). Epigenetics includes abnormal DNA methylation and histone modification, which affects the expression of immune genes and inflammation progression, has become a hot spot to explain the 3 pathogenesis of RA (Mazzone et al, 2019).…”