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MicroRNA-194 is a target of transcription factor 1 (Tcf1, Hnf1α) in adult liver and controls expression of frizzled-6

Krützfeldt, Jan and Rösch, Nora and Hausser, Jean and Manoharan, Muthiah and Zavolan, Mihaela and Stoffel, Markus. (2012) MicroRNA-194 is a target of transcription factor 1 (Tcf1, Hnf1α) in adult liver and controls expression of frizzled-6. Hepatology, Vol. 55, No. 1. pp. 98-107.

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Official URL: http://edoc.unibas.ch/dok/A5844669

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Abstract

Transcription factor 1 (Tcf1; Hepatocyte nuclear factor 1α [Hnf1α]) is critical for hepatocyte development and function. Whether Tcf1 also regulates hepatic microRNAs (miRs) has not been investigated yet. Here, we analysed Tcf1-dependent microRNA expression in adult mice in which this transcription factor had been genetically deleted (Tcf1−/–) using microRNA microarray analysis. The miR-192/-194 cluster was markedly downregulated in liver of Tcf1−/– mice. MiR-192/-194 levels were also decreased in two other tissues, which express Tcf1, kidney and small intestine, although to a lesser extent than in liver. In order to identify targets of miR-192/-194 in vivo we combined Affymetrix gene analysis of liver in which miR-192/-194 had been silenced or overexpressed, respectively, and tested regulated mRNAs with multiple binding sites for these microRNAs. This approach revealed frizzled-6 (Fzd6) as robust endogenous target of miR-194. MiR-194 also targets human FZD6 and expression of miR-194 and Fzd6 are inversely correlated in a mouse model of hepatocellular carcinoma (Dgcr8flox/flox p53flox/flox x Alb-Cre). Conclusion: Our results support a role of miR-194 in liver tumorigenesis through its endogenous target Fzd6. These results may have important implications for Tcf1-mediated liver proliferation. (HEPATOLOGY 2011)
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (Zavolan)
UniBasel Contributors:Zavolan, Mihaela
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Saunders
ISSN:0270-9139
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:16 Aug 2013 07:32
Deposited On:14 Sep 2012 06:42

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