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

Veronese A, Visone R, Consiglio J, Acunzo M, Lupini L, Kim T, Ferracin M, Lovat F, Miotto E, Balatti V, D'Abundo L, Gramantieri L, Bolondi L, Pekarsky Y, Perrotti D, Negrini M, Croce CM
Proc Natl Acad Sci U S A. 2011 108 (12): 4840-5

PMID: 21383185 · PMCID: PMC3064338 · DOI:10.1073/pnas.1101734108

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.

MeSH Terms (12)

Apoptosis Regulatory Proteins beta Catenin Cell Line, Tumor Genetic Loci HEK293 Cells Humans Insulin-Like Growth Factor II Introns MicroRNAs Mutation Proto-Oncogene Proteins Transcription Factors

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