Mutated beta-catenin evades a microRNA-dependent regulatory 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 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.

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