MicroRNA-200b regulates preadipocyte proliferation and differentiation by targeting KLF4

Biomed Pharmacother. 2018 Jul:103:1538-1544. doi: 10.1016/j.biopha.2018.04.170. Epub 2018 May 7.

Abstract

MicroRNAs (miRNAs) are small, non-coding RNAs that affect the post-transcriptional regulation of a variety of biological pathways. A previous study found out that miR-200b was important in the metabolism of obesity, but the mechanism of miR-200b regulateing adipogenesis is not fully understood.. In the present study, we observed that miR200b expression decreased both in obese mice and during the process of 3T3-L1 adipogenic differentiation. Overexpression of miR-200b promoted adipocyte proliferation by regulating the expression of cell cycle-regulated factors.Furthermore, overexpression of miR-200b reduced lipid accumulation and triglyceride content in adipocytes, and accompanied by a marked decrease in the expression of adipocyte-specific genes involved in fatty acid synthesis. Luciferase activity assays confirmed that miR-200b regulated adipocyte differentiation by directly targeting KLF4, and miR-200b suppressed the expression of KLF4 in both mRNA level and protein level. Moreover, the expression levels of downstream genes of KLF4, such as C/EBPβ, C/EBPα, KLF5 and PPARγ, were decreased in 3T3-L1 cells by miR-200b overexpression. Taken together, these results indicate that miR-200b may be involved in adipogenesis and could be a target for therapeutic intervention in obesity and metabolic syndrome.

Keywords: Adipocytes; Differentiation; KLF4; Proliferation; microRNA-200b.

MeSH terms

  • 3' Untranslated Regions / genetics
  • 3T3-L1 Cells
  • Adipocytes / cytology*
  • Adipocytes / metabolism*
  • Adipogenesis / genetics
  • Animals
  • Base Sequence
  • Cell Differentiation* / genetics
  • Cell Proliferation
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / metabolism*
  • Male
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Models, Biological

Substances

  • 3' Untranslated Regions
  • Klf4 protein, mouse
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • MicroRNAs
  • Mirn200 microRNA, mouse