Regulation of N-Myc downstream regulated gene 2 by bile acids

•Bile acid CDCA induces tumor suppressor NDRG2 expression in hepatocytes.•Induction of NDRG2 by bile acids requires FXR expression.•An intronic FXR-response element was identified in human and murine genes.•FXR activation increases NDRG2 mRNA and protein levels in kidney.•We provide knowledge toward...

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Bibliographic Details
Published in:	Biochemical and biophysical research communications Vol. 434; no. 1; pp. 102 - 109
Main Authors:	Langhi, Cédric, Pedraz-Cuesta, Elena, Donate, Yolanda, Marrero, Pedro F., Haro, Diego, Rodríguez, Joan C.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 26-04-2013 Elsevier B.V
Subjects:	Animals Bile acids Bile Acids and Salts - pharmacology Cancer Cell Line, Tumor Càncer FXR Gene Expression Regulation, Neoplastic - drug effects Gene Knockdown Techniques Genetic regulation Hep G2 Cells Humans Kidney Male Metabolism Metabolisme Mice Mice, Inbred C57BL Mice, Knockout NDRG2 Nuclear receptor Nuclear receptors (Biochemistry) Proteins Proteins - genetics Proteins - metabolism Proteïnes Receptors nuclears (Bioquímica) Receptors, Cytoplasmic and Nuclear - agonists Receptors, Cytoplasmic and Nuclear - antagonists & inhibitors Receptors, Cytoplasmic and Nuclear - genetics Regulació genètica Ronyó Tumor Suppressor Proteins - genetics Tumor Suppressor Proteins - metabolism Up-Regulation - physiology Àcids biliars CDCA FXR Nuclear receptor Bile acids MOI QPCR HCC IR1 siRNA ENaC NDRG2 Metabolism RXR Kidney TSS EMSA TK SHP I-BABP PLTP Cancer
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Summary:	•Bile acid CDCA induces tumor suppressor NDRG2 expression in hepatocytes.•Induction of NDRG2 by bile acids requires FXR expression.•An intronic FXR-response element was identified in human and murine genes.•FXR activation increases NDRG2 mRNA and protein levels in kidney.•We provide knowledge toward the understanding of NDRG2 physiological function. Here we report that bile acid chenodeoxycholic acid (CDCA) and synthetic farnesoid X receptor (FXR) agonist GW4064 robustly induced tumor suppressor N-Myc downstream regulated gene 2 (NDRG2) expression in human hepatoma cells and primary hepatocytes. Knockdown of FXR abolished the induction by CDCA, whereas overexpression of a constitutively active form of FXR increased NDRG2 expression. A FXR-response element was identified within intronic regions of human and murine genes. Moreover, mice given GW4064 exhibit an increase of Ndrg2 expression in liver and kidney, where both NDRG2 and FXR are enriched. The identification of NDRG2 as a bile acid regulated gene may provide novel knowledge toward the understanding of NDRG2 physiological function and the link between metabolism and cancer.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0006-291X 1090-2104
DOI:	10.1016/j.bbrc.2013.03.058