MicroRNA-214-3p Targeting Ctnnb1 Promotes 3T3-L1 Preadipocyte Differentiation by Interfering with the Wnt/β-Catenin Signaling Pathway

Int J Mol Sci. 2019 Apr 12;20(8):1816. doi: 10.3390/ijms20081816.

Abstract

Differentiation from preadipocytes into mature adipocytes is a complex biological process in which miRNAs play an important role. Previous studies showed that miR-214-3p facilitates adipocyte differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) in vitro. The detailed function and molecular mechanism of miR-214-3p in adipocyte development is unclear. In this study, the 3T3-L1 cell line was used to analyze the function of miR-214-3p in vitro. Using 5-Ethynyl-2'-deoxyuridine (EdU) staining and the CCK-8 assay, we observed that transfection with the miR-214-3p agomir visibly promoted proliferation of 3T3-L1 preadipocytes by up-regulating the expression of cell cycle-related genes. Interestingly, overexpression of miR-214-3p promoted 3T3-L1 preadipocyte differentiation and up-regulated the expression of key genes for lipogenesis: PPARγ, FABP4, and Adiponectin. Conversely, inhibition of miR-214-3p repressed 3T3-L1 preadipocyte proliferation and differentiation, and down-regulated the expression of cell cycle-related genes and adipogenic markers. Furthermore, we proved that miR-214-3p regulates 3T3-L1 preadipocyte differentiation by directly targeting the 3'-untranslated regions (3'UTR) of Ctnnb1, which is an important transcriptional regulatory factor of the Wnt/β-Catenin pathway. Taken together, the data indicate that miR-214-3p may positively regulate preadipocyte proliferation and enhance differentiation through the Wnt/β-Catenin signaling pathway.

Keywords: Ctnnb1; adipogenesis; differentiation; miR-214-3p; proliferation.

MeSH terms

  • 3' Untranslated Regions
  • 3T3-L1 Cells
  • Adipocytes / cytology*
  • Adipocytes / metabolism*
  • Adipogenesis / genetics
  • Animals
  • Base Sequence
  • Cell Differentiation / genetics*
  • Cell Proliferation
  • Mice
  • MicroRNAs / genetics*
  • RNA Interference
  • Wnt Signaling Pathway*
  • beta Catenin / genetics*

Substances

  • 3' Untranslated Regions
  • CTNNB1 protein, mouse
  • MicroRNAs
  • Mirn214 microRNA, mouse
  • beta Catenin