MicroRNA-489-3p promotes adipogenesis by targeting the Postn gene in 3T3-L1 preadipocytes

Life Sci. 2021 Aug 1:278:119620. doi: 10.1016/j.lfs.2021.119620. Epub 2021 May 15.

Abstract

Aims: Accumulating evidence indicates that a number of microRNAs (miRNAs) serve as essential regulators during adipogenesis and adipolysis in humans and animals and play critical roles in the development of fat tissue. In this study, we aimed to determine the functional role and underlying regulatory mechanism of microRNA-489-3p (miR-489) in adipocytes.

Materials and methods: The expression patterns of miR-489 in mice were measured by qRT-PCR. Overexpression and knockdown of miR-489 by mimic and inhibitor transfections in 3T3-L1 preadipocytes revealed the regulatory effect of miR-489 on cellular proliferation and differentiation and energy turnover. Furthermore, RNA-seq, bioinformatics prediction, and dual luciferase reporter assays were used to identify the direct target of miR-489.

Key findings: The results showed that miR-489 was highly expressed in the visceral fat tissue of adult mice, and obese mice exhibited higher levels of miR-489 than normal mice. Overexpression of miR-489 suppressed proliferation but promoted adipogenic differentiation and lipid accumulation in the cells. Mitochondrial oxidation also fluctuated in the cells due to the high expression of miR-489. Notably, knockdown of miR-489 did not have a strong opposing effect on the cells. Periostin (Postn) was identified as a direct target gene for miR-489, and silencing the Postn gene similarly stimulated adipogenesis and differentiation of adipocytes.

Significance: miR-489 provides a strong driving force for adipogenesis metabolism and adipocyte differentiation by targeting the Postn gene. This result may contribute to the treatment of obesity.

Keywords: Differentiation; Postn; Preadipocyte; Regulatory mechanism; miR-489.

MeSH terms

  • Adipocytes / metabolism
  • Adipocytes / pathology*
  • Adipogenesis*
  • Animals
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Cycle
  • Cell Differentiation
  • Cell Proliferation
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Mice
  • Mice, Obese
  • MicroRNAs / genetics*
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Obesity / genetics
  • Obesity / metabolism
  • Obesity / pathology*

Substances

  • Cell Adhesion Molecules
  • MIRN489 microRNA, mouse
  • MicroRNAs
  • Postn protein, mouse