miR-148b-3p affects the pathogenesis of adjuvant-induced arthritis rats through the direct target DNMT1.

Our previous study showed that up-regulated DNA methyltransferase-1 (DNMT1) played an important role in the hypermethylation modification of SFRP4 in adjuvant-induced arthritis (AIA) rats. This work focused on the role of disordered miR-148b-3p in RA pathology and its corresponding regulatory targets. The expression of miR-148b-3p and DNMT1, and the effect of miR-148b-3p on the DNMT1 expression were determined by real-time qPCR, western blotting and double luciferase reporter genes. The role of miR-148b-3p on the SFRP4 expression, the canonical Wnt signaling and the pathology of AIA rats was investigated using real-time qPCR, western blotting and methylation-specific PCR (MSP). The results showed that the expression of miR-148b-3p was significantly decreased, the expression of DNMT1 was significantly increased and the DNMT1 was the direct target of miR-148b-3p in AIA rats compared with normal group. Transfection of miR-148b-3p mimics up-regulated the SFRP4 expression, inhibited the canonical Wnt signaling and the pathogenesis of AIA rats by targeting the DNMT1. The role of miR-148b-3p knockdown was opposite to that of miR-148b-3p overexpression. These results suggest that miR-148b-3p may influence the pathogenesis of RA with the DNMT1 as a direct target and miR-148b-3p may be a potential diagnostic and therapeutic target for RA patients.