Mutated β-catenin evades a microRNA-dependentregulatory loop

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 beta-catenin through an interaction with the basic helix-loop-helix protein upstream stimulatory transcription factor 1. We also show that beta-catenin itself is a target of miR-483-3p, triggering a negative regulatory loop that becomes ineffective in cells harboring an activating mutation of beta-catenin. These results provide insights into the complex regulation of the IGF2/miR-483 locus, revealing players in the beta-catenin pathway.