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Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4840-5. doi: 10.1073/pnas.1101734108. Epub 2011 Mar 7.

Mutated beta-catenin evades a microRNA-dependent regulatory loop.

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  • 1Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA.

Abstract

hsa-mir-483 is located within intron 2 of the IGF2 gene. We have previously shown oncogenic features of miR-483-3p through cooperation with IGF2 or by independently targeting the proapoptotic gene BBC3/PUMA. Here we demonstrate that expression of miR-483 can be induced independently of IGF2 by the oncoprotein β-catenin through an interaction with the basic helix-loop-helix protein upstream stimulatory transcription factor 1. We also show that β-catenin itself is a target of miR-483-3p, triggering a negative regulatory loop that becomes ineffective in cells harboring an activating mutation of β-catenin. These results provide insights into the complex regulation of the IGF2/miR-483 locus, revealing players in the β-catenin pathway.

PMID:
21383185
[PubMed - indexed for MEDLINE]
PMCID:
PMC3064338
Free PMC Article
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