miR-709 inhibits 3T3-L1 cell differentiation by targeting GSK3β of Wnt/β-catenin signaling

Adipocyte differentiation is tightly regulated by altering gene expression in which microRNAs might be strong post-transcriptional regulators. In this study, we examined the roles of miR-709 in adipogenic differentiation of 3T3-L1 preadipocyte. We found that miR-709 expression was down-regulated during adipogenesis after MDI (1-methyl-3-isobutylxanthine, dexamethasone and insulin) stimulation in normal cultured 3T3-L1 cells, while up-regulated after Lid I treatment. Overexpression of miR-709 inhibited adipogenic differentiation of 3T3-L1 cells. We demonstrated that miR-709 directly targeted 3' UTR of GSK3 beta (glycogen synthase kinase 3 beta). Overexpression of miR-709 decreased GSK3 beta protein but not mRNA level. Furthermore, the inhibition of miR-709 could be counteracted by overexpression of GSK3 beta during 3T3-L1 adipogenic differentiation. In addition, miR-709 increased both protein and mRNA levels of beta-catenin, which is the downstream effector of GSK3 beta in Wnt/beta-catenin signaling pathway, and subsequently elevated the expression of target of beta-catenin which represses adipogenesis. These data indicate that miR-709 inhibits adipocyte differentiation through targeting GSK3 beta and subsequently activating Wnt/beta-catenin signaling pathway. (C) 2014 Elsevier Inc. All rights reserved.