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

Y Zhang, Z Yang, R Whitby, L Wang - Biochemical and biophysical …, 2011 - Elsevier
Y Zhang, Z Yang, R Whitby, L Wang
Biochemical and biophysical research communications, 2011Elsevier
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 …
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.
Elsevier