Association of MTMR3 rs12537 at miR-181a binding site with rheumatoid arthritis and systemic lupus erythematosus risk in Egyptian patients

Abstract

Single nucleotide polymorphisms (SNPs) in microRNA-target sites influence an individual’s risk and prognosis for autoimmune diseases. Myotubularin-related protein 3 (MTMR3), an autophagy-related gene, is a direct target of miR-181a. We investigated whether MTMR3 SNP rs12537 in the miR-181a-binding site is associated with the susceptibility and progression of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Overall, 94 patients with RA, 80 patients with SLE, and 104 healthy volunteers were recruited. Genotyping and expression analysis of circulating MTMR3 and miR-181a were performed by qPCR. The autophagic marker MAP1LC3B was measured by ELISA. The rs12537 minor homozygote (TT) genotype was a candidate risk factor of both RA and SLE. rs12537TT was associated with lower serum MTMR3 expression and higher LC3B levels than other genotypes in patients with both diseases. Serum miR-181a expression was higher in rs12537TT carriers than in other genotypes among SLE patients. Serum miR-181a and MTMR3 levels were inversely correlated in SLE but not in RA patients. rs12537TT and serum miR-181a were positively associated with disease severity in both diseases. Our results identify a novel role of rs12537 in the susceptibility and progression of RA and SLE, possibly through impacting the interaction between miR-181a and MTMR3 leading to increased autophagy.

Serum a proliferation-inducing ligand and MicroRNA-223 are associated with rheumatoid arthritis: diagnostic and prognostic implications

“…The genesis of RA involves complex multifactorial steps in which an interplay exists between genetic, epigenetic, immunological and environmental factors, but knowledge of the full molecular basis of RA is still incomplete (Senousy et al 2019 ). In addition, the current diagnostic methods of RA are unreliable and lack sufficient sensitivity and specificity.…”

“…miRNAs can control many immune processes, including T- and B-cell development and maturation, antigen presentation, Toll-like receptor signaling and pro-inflammatory cytokine production, immunoglobulin class-switch recombination in B-cells, and T-cell receptor signaling (Ceribelli et al 2012 ). Differential expression of non-coding RNAs, including miRNAs were found in patients affected by several autoimmune diseases, and were linked to the pathogenesis of these conditions (Senousy et al 2019 ; Senousy et al 2020 ; Abd-Elmawla et al 2020 ). Indeed, dysregulated miRNA expression has been shown to be implicated into the molecular mechanisms of RA (Tavasolian et al 2018 ).…”

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

“…MicroRNAs (miRNAs) are small endogenous non-coding single-stranded RNAs, with a length of about 22 nucleotides, which are involved in the post-transcriptional regulation of gene expression. In recent years, accumulating studies have demonstrated that miRNAs play a key role in various cancers (He et al, 2011;Lin et al, 2013;Zhang et al, 2015;Ding et al, 2016;Fan et al, 2017) as well as autoimmune diseases, including RA, systemic lupus erythematosus (SLE) (Xie and Xu, 2018;Senousy et al, 2019), sjogren's syndrome (SS) (Jang et al, 2019), and systemic sclerosis (Iwamoto et al, 2016). In this review, we systematically summarize the recent advances on the role of miRNAs in RA, with special emphasis on how the genetic variants and expression variations correlate to the susceptibility to and pathogenesis of RA, based on different inflammation-related cells, inflammatory cytokines, and inflammatory signaling pathways (Figure 1).…”

Serum A Proliferation-Inducing Ligand and MicroRNA-223 are Associated with Rheumatoid Arthritis: Diagnostic and Prognostic Implications

“…The genesis of RA involves complex multifactorial steps in which an interplay exists between genetic, epigenetic, immunological and environmental factors, but knowledge of the full molecular basis of RA is still incomplete [3]. In addition, the current diagnostic methods of RA are unreliable and lack su cient sensitivity and speci city.…”

“…miRNAs can control many immune processes, including T-and B-cell development and maturation, antigen presentation, Toll-like receptor signaling and pro-in ammatory cytokine production, immunoglobulin class-switch recombination in B-cells, and T-cell receptor signaling [6]. Differential expression of non-coding RNAs, including miRNAs were found in patients affected by several autoimmune diseases, and were linked to the pathogenesis of these conditions [3,7,8]. Indeed, dysregulated miRNA expression has been shown to be implicated into the molecular mechanisms of RA [9].…”