Interference RNA and microRNA in Rheumatoid Arthritis: Diagnostic Biomarkers, Epigenetic Regulation, and Emerging Therapeutic Strategies

Rheumatoid arthritis (RA) is a persistent autoimmune disorder where traditional serological indicators, including rheumatoid factor and anti-citrullinated protein antibodies, are inadequate for early and precise diagnosis, and existing anti-cytokine treatments have effectiveness and safety constraints. Recent data indicates that non-coding microRNAs (miRNAs) play a crucial role in the epigenetic control of inflammatory and catabolic pathways in the synovium, cartilage, and circulating immune cells, therefore facilitating the development and progression of RA. This review delineates the diagnostic efficacy of circulating and cell-associated miRNAs, specifically miR-16, miR-132, miR-146a, miR-155, and miR-223, which exhibit aberrant expression in peripheral blood mononuclear cells and T-lymphocyte subsets, while assessing early-stage rheumatoid arthritis signatures identified through array-based profiling. The study examines the interaction of RNA interference, DNA methylation, and histone changes in the regulation of matrix-degrading enzymes like MMP-13 and ADAMTS4, emphasizing how modified epigenetic patterns in osteoarthritis and rheumatoid arthritis contribute to joint degradation. This review examines mechanistic and preclinical data on miR‑124a, miR‑146a, miR‑210, and miR‑27b, demonstrating how miRNA mimics or inhibitors can influence cytokine networks, NF‑κβ signalling, DDR2-mediated cartilage degradation, and synovial fibroblast proliferation, thereby providing a basis for miRNA-based disease-modifying therapies. While proof-of-concept studies demonstrate the viability of miRNA-targeted diagnostics and therapeutics, considerable efforts are necessary to validate comprehensive biomarker panels, enhance delivery systems, and guarantee long-term safety, thereby facilitating the effective integration of miRNA-guided precision medicine into rheumatoid arthritis management.