The role of miR-125a-5p in predicting the clinical response in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disorder that poses treatment challenges and displays considerable inter-individual variability in therapeutic responses. This research investigated the potential of miR-125a-5p as a biomarker for evaluating the disease activity and predicting the therapeutic responses in RA, and further explored the underlying mechanisms through in vitro experiments. This study enrolled 137 RA patients and 101 healthy individuals, measured serum miR-125a-5p expression level by RT-qPCR, analyzed correlations with clinical indices, and followed patients for 3 months to evaluate remission. TNF-α-induced HFLS cells were employed to explore the effects of miR-125a-5p on cell functions and inflammation/oxidative stress. The results showed serum miR-125a-5p was reduced in RA patients compared with healthy individuals, declining progressively with increasing disease activity, and was negatively correlated with RF, CRP, ESR, Anti-CCP, DAS28 score, SJC, and TJC. Serum miR-125a-5p demonstrated favorable diagnostic performance in discriminating RA. Elevated miR-125a-5p levels were observed in the clinical remission group, and its low expression independently predicted failure to achieve clinical remission in RA patients. The in vitro findings further indicated that reduced miR-125a-5p expression in RA patients might relieve the suppression of proliferation, migration, and invasion of TNF-α-induced HFLS cells, and promote inflammatory factors release and oxidative stress damage, thereby accelerating the progression of RA. Serum miR-125a-5p represents a promising novel biomarker for early diagnosis, disease progression monitoring, and clinical treatment response prediction in RA. miR-125a-5p is a potential therapeutic target, and it effectively delays RA progression by suppressing the abnormal activation of HFLS cells.