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

Abstract

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.

Keywords:

• Adjuvant-induced arthritis
• miR-148b-3p
• DNA methyltransferase-1
• SFRP4
• canonical Wnt signaling

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This project was supported by the National Science Foundation of China (No. 81302783) and the Stable Talent Personnel Project of Anhui Science and Technology University (No. ZRC2014473).