Oncogenic role of miR-483-3p at the IGF2/483 locus.

Abstract

hsa-mir-483 is located within intron 2 of the IGF2 locus. We found that the mature microRNA (miRNA) miR-483-3p is overexpressed in 100% of Wilms' tumors. In addition, colon, breast, and liver cancers exhibit high or even extremely high levels of miR-483-3p in approximately 30% of the cases. A coregulation with IGF2 mRNA was detected, although some tumors exhibited high expression of miR-483-3p without a concomitant increase of IGF2. These findings suggested that miR-483-3p could cooperate with IGF2 or act as an autonomous oncogene. Indeed, here we prove that an anti-miRNA oligonucleotide against miR-483-3p could inhibit the miRNAs without affecting IGF2 mRNA and it could suppress tumorigenicity of HepG2 cells, a cell line that overexpresses miR-483-3p and IGF2. Conversely, no antitumor effect was elicited by inhibition of IGF2. The oncogenic mechanism of miR-483-3p was at least partially clarified by the finding that it could modulate the proapoptotic protein BBC3/PUMA and miR-483-3p enforced expression could protect cells from apoptosis. Our results indicate that miR-483-3p could function as an antiapoptotic oncogene in various human cancers and reveal a new, potentially important target for anticancer therapy.

Authors
  • Alder H
  • Angioni A
  • Bolondi L
  • Consiglio J
  • Croce CM
  • D'Elia G
  • Ferracin M
  • Fornari F
  • Gramantieri L
  • Lanza G
  • Lupini L
  • Negrini M
  • Querzoli P
  • Veronese A
  • Visone R
  • Zanesi N
PubMed ID
Appears In
Cancer Res, 2010, 70 (8)