miR-330-5p inhibits H2O2-induced adipogenic differentiation of MSCs by regulating RXRγ

The elucidation of the underlying molecular mechanism of H2O2-induced adipocyte differentiation in mesenchymal stem cells (MSCs) is important for the development of treatments for metabolic diseases. The aim of the present study was to identify microRNA (miR)-330-5p, which targets retinoid X receptor y (RXR gamma) and to determine the function of H2O2-induced adipogenic differentiation of MSCs. During differentiation of MSCs into adipocytes induced by H2O2, miR-330-5p expression was decreased with a concomitant increase in RXR gamma expression. A luciferase assay with RXR gamma 3'-untranslated region (UTR) reporter plasmid, including the miR-330-5p-binding sequences, identified that the introduction of miR-330-5p decreases luciferase activity. However, it did not affect the activity of mutated RXR gamma 3'-UTR reporter. Enforced expression of miR-330-5p significantly inhibited adipocyte differentiation by decreasing RXR gamma mRNA and protein levels. In contrast, inhibition of the endogenous miR-330-5p promoted the formation of lipid droplets by rescuing RXR gamma expression. Furthermore, the effects of inhibition of RXR gamma were similar to those of overexpression of miR-330-5p on H2O2-induced adipogenic differentiation from MSCs. miR-330-5p inhibits H2O2-induced adipogenic differentiation of MSCs, and this is dependent on RXR gamma. Taken together, the results of the present study revealed that miR-330-5p acts as a critical regulator of RXR gamma, and is able to determinate the fate of MSCs to differentiate into adipocytes. This suggests that miR-330-5p and RXR gamma may be target molecules for controlling metabolic diseases.