Regulation of miR-200c by nuclear receptors PPAR{alpha}, LRH-1 and SHP
- Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84132 (United States)
- Department of Chemistry, University of Southampton, Southampton, Hants SO17 1BJ (United Kingdom)
Highlights: Black-Right-Pointing-Pointer Knockdown of PPAR{alpha} and LRH-1 abolishes miR-200c inhibition of HCC cell migration. Black-Right-Pointing-Pointer SHP represses miR-200c expression via inhibition of the activity of PPAR{alpha} and LRH-1. Black-Right-Pointing-Pointer RJW100 exhibits strong ability to downregulate ZEB1 and ZEB2 proteins. -- 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 PPAR{alpha} and LRH-1 siRNAs. The expression of miR-200c was decreased by PPAR{alpha}/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 PPAR{alpha} 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.
- OSTI ID:
- 22207597
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 416, Issue 1-2; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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