MicroRNA-125a-5p Mediates 3T3-L1 Preadipocyte Proliferation and Differentiation

Molecules. 2018 Feb 2;23(2):317. doi: 10.3390/molecules23020317.

Abstract

Excessive accumulation of adipose tissue is a main cause of obesity or overweight, which is significantly involved in increasing the risk of diseases. Recently, numerous studies have proved that microRNAs (miRNAs) play important roles in adipogenesis by negatively regulating gene expression at posttranscriptional levels. In this study, we showed that miR-125a-5p was expressed at lower levels in the adipose tissues of high-fat diet (HFD)-fed mice than the normal chow (NCW)-fed mice. MiR-125a-5p expression were strongly up-regulated by nearly five-fold, when 3T3-L1 preadipocyte were induced and differentiated into mature adipocytes. Functional analysis indicated that overexpression of miR-125a-5p promoted 3T3-L1 preadipocyte proliferation and inhibited its differentiation. By contrast, inhibition of miR-125a-5p repressed 3T3-L1 preadipocyte proliferation and accelerated its differentiation. Furthermore, a dual-luciferase reporter assay demonstrated that signal transducer and activator of transcription 3 (STAT3) is a direct target gene of miR-125a-5p during 3T3-L1 preadipocyte differentiation. Further analysis confirmed that the process of miR-125a-5p inhibiting 3T3-L1 preadipocyte differentiation might be associated with the regulation of fatty acid metabolism related genes. Taken together, our results indicated that miR-125a-5p might promote 3T3-L1 preadipocyte proliferation, whereas inhibiting 3T3-L1 preadipocyte differentiation by negatively regulating STAT3.

Keywords: 3T3-L1; STAT3; miR-125a-5p; obesity; preadipocyte.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism*
  • Adipocytes / pathology
  • Adipogenesis / genetics*
  • Adipose Tissue / metabolism*
  • Adipose Tissue / pathology
  • Animals
  • Antagomirs / genetics
  • Antagomirs / metabolism
  • Base Sequence
  • Binding Sites
  • Cell Proliferation
  • Diet, High-Fat / adverse effects
  • Gene Expression Regulation
  • Genes, Reporter
  • Lipid Metabolism / genetics
  • Luciferases / genetics
  • Luciferases / metabolism
  • Male
  • Mice
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Obesity / etiology
  • Obesity / genetics*
  • Obesity / metabolism
  • Obesity / pathology
  • STAT3 Transcription Factor / genetics*
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction

Substances

  • Antagomirs
  • MicroRNAs
  • Mirn125 microRNA, mouse
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Luciferases