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

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.

► Knockdown of PPARα and LRH-1 abolishes miR-200c inhibition of HCC cell migration.
► SHP represses miR-200c expression via inhibition of the activity of PPARα and LRH-1.
► RJW100 exhibits strong ability to downregulate ZEB1 and ZEB2 proteins.