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

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

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  • 1Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.


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.

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