Regulation of miR-200c by nuclear receptors PPARα, LRH-1 and SHP

Biochem Biophys Res Commun. 2011 Dec 9;416(1-2):135-9. doi: 10.1016/j.bbrc.2011.11.011. Epub 2011 Nov 11.

Abstract

We investigated regulation of miR-200c expression by nuclear receptors. Ectopic expression of miR-200c inhibited MHCC97H cell migration, which was abrogated by the synergistic effects of PPARα and LRH-1 siRNAs. The expression of miR-200c was decreased by PPARα/LRH-1 siRNAs and increased by SHP siRNAs, and overexpression of the receptors reversed the effects of their respective siRNAs. SHP siRNAs also drastically enhanced the ability of the LRH-1 agonist RJW100 to induce miR-200c and downregulate ZEB1 and ZEB2 proteins. Co-expression of PPARα and LRH-1 moderately transactivated the miR-200c promoter, which was repressed by SHP co-expression. RJW100 caused strong activation of the miR-200c promoter. This is the first report to demonstrate that miR-200c expression is controlled by nuclear receptors.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Humans
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • PPAR alpha / genetics
  • PPAR alpha / metabolism*
  • Promoter Regions, Genetic
  • RNA, Small Interfering / genetics
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Transcriptional Activation

Substances

  • MIRN200 microRNA, human
  • MicroRNAs
  • NR5A2 protein, human
  • PPAR alpha
  • RNA, Small Interfering
  • Receptors, Cytoplasmic and Nuclear
  • nuclear receptor subfamily 0, group B, member 2