miR-330-5p inhibits H(2)O(2)-induced adipogenic differentiation of MSCs by regulating RXRγ

The elucidation of the underlying molecular mechanism of H(2)O(2)-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 γ (RXRγ) and to determine the function of H(2)O(2)-induced adipogenic differentiation of MSCs. During differentiation of MSCs into adipocytes induced by H(2)O(2), miR-330-5p expression was decreased with a concomitant increase in RXRγ expression. A luciferase assay with RXRγ 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 RXRγ 3′-UTR reporter. Enforced expression of miR-330-5p significantly inhibited adipocyte differentiation by decreasing RXRγ mRNA and protein levels. In contrast, inhibition of the endogenous miR-330-5p promoted the formation of lipid droplets by rescuing RXRγ expression. Furthermore, the effects of inhibition of RXRγ were similar to those of overexpression of miR-330-5p on H(2)O(2)-induced adipogenic differentiation from MSCs. miR-330-5p inhibits H(2)O(2)-induced adipogenic differentiation of MSCs, and this is dependent on RXRγ. Taken together, the results of the present study revealed that miR-330-5p acts as a critical regulator of RXRγ, and is able to determinate the fate of MSCs to differentiate into adipocytes. This suggests that miR-330-5p and RXRγ may be target molecules for controlling metabolic diseases.