Etanercept suppresses rheumatoid arthritis development via modulating miR-125a-3p.

Although etanercept is effective in managing inflammatory disorders, its precise anti-inflammatory mechanisms remain unclear. This study explored its therapeutic benefits in rheumatoid arthritis (RA) by focusing on the modulation of miR-125a-3p. Viability, apoptosis, and miR-125a-3p expression in MH7A cells, a human rheumatoid arthritis synovial fibroblast cell line, were determined using CCK-8 assay, flow cytometry, and RT-qPCR, respectively. Inflammatory factors, lipid peroxidation levels, apoptosis/ferroptosis-related proteins, and PI3K/AKT/mTOR pathway activation were measured by ELISA and Western blot; bioinformatics analysis was used to predict relevant pathways. Etanercept inhibited MH7A cell viability, promoted apoptosis and ferroptosis, and exerted anti-inflammatory effects, which were abolished by miR-125a-3p inhibitor, partially via the PI3K/AKT/mTOR pathway. miR-125a-3p was downregulated in MH7A cells and RA patients but upregulated following etanercept treatment. This study demonstrates that etanercept has therapeutic potential against RA by modulating miR-125a-3p, providing a promising therapeutic target.