title: Regulation of miR-200c by nuclear receptors PPARα, LRH-1 and SHP.
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.
authors.affiliation: Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Yang
authors.forename: Richard
authors.initials: R
authors.lastname: Whitby
authors.forename: Li
authors.initials: L
authors.lastname: Wang
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics*; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: C533896:MIRN200 microRNA, human; D035683:MicroRNAs; C082631:NR5A2 protein, human; D047493:PPAR alpha; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; C099713:nuclear receptor subfamily 0, group B, member 2
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