Identification of putative miRNA biomarkers in early rheumatoid arthritis by genome-wide microarray profiling: A pilot study

Abstract

Despite the existing research, the etiology of rheumatoid arthritis (RA), an autoimmune disease remains poorly understood with early and accurate diagnosis difficult to achieve. MicroRNAs (miRNAs) play an important role in biological processes as modulators of transcription and translation. Previous studies have demonstrated a downregulation of several genes in early RA stages and in addition, miRNAs may serve as early biomarkers of subclinical changes in early RA.When comparing the four groups (ANOVA P<0.01, fold change >4), we found 253 differentially expressed miRNAs. Of these, 97 miRNAs were identified as overexpressed in early rheumatoid arthritis. The validation of miRNA microarray expression was performed in a set by RT-qPCR and showed strong agreement with microarray expression data. The putative targets of overexpressed microRNAs in early RA were significantly enriched in apoptosis, tolerance loss and Wnt pathways.Moreover, ROC analysis showed values of AUC 0.76 and p<0.05 for miR361-5p, identifying this miRNA as a potential biomarker of disease.We identified specific microRNAs associated with early rheumatoid arthritis and proposed them as early biomarkers of disease. Our results provide novel insight into immune disease physiopathology and describe unreported microRNAs in RA with potential for clinical use.

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

“…miR-223 is highly expressed in naive CD4 + T cell, but hardly expressed in Th17 (59). Overexpression of miR-361-5p in early RA was associated with T cell activation and inflammatory response (45). These special expressions may be involved in the pathogenesis of RA, which deserve further research.…”

“…The expression of miR-371b, miR-483, miR-642b is significantly up-regulated while miR-25, miR-378d are down-regulated in PBMC that eventually developed from early undifferentiated arthritis (EUA) into RA (77). Meanwhile, miR-22 (78), miR-361-5p (45) and miR-223-3p (45) are significantly up-regulated in high-risk or CCP positive populations. Therefore, miR-642b-5p, miR-483-3p, miR-371b-5p, miR-25-3p, miR-378d, miR-22, miR-361-5p and miR-223-3p can be used as biomarkers for early diagnosis of RA.…”

“…Interestingly, the expression of miR-146a reduced in T-reg cells during high activity of RA, by targeting STAT1, resulting the proinflammatory phenotype of T-reg cells (36). Besides that, the high level of miR-99b-5p (40), miR-361-5p (45) and miR-17 (46) participated in enhancing T cell proliferation and differentiation, anti-apoptosis. miR-99b-5p in peripheral blood mononuclear cells (PBMCs) was found to decrease the expression of mTOR and RASSF4 genes to inhibit T cell apoptosis, promoted T cell proliferation and inflammatory response (40).…”

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

“…The expression of miR-223 is high in naive CD4 + T cell, but hardly expressed in Th17 (Fulci et al, 2010). Overexpression of miR-361-5p in early RA is associated with T cell activation and inflammatory response (Romo-Garcia et al, 2019). Overall, miRNAs cooperate with other non-coding RNAs (ncRNAs) to alter the DNA methylation and/or expression of their targets, thus regulating innate and adaptive immune cell differentiation and apoptosis, and ultimately influencing the inflammatory and autoimmune response in RA.…”

Relationship of miRNA-146a to systemic lupus erythematosus

“…The exact cause of SLE remains elusive, however, evidence suggests that miRNA is involved in its pathogenesis. [ 6 7 ] miRNA is an important molecule involved in the regulation of gene expression. They are evolutionally conserved single-stranded noncoding RNAs that function in post-transcriptional regulation of gene expression.…”