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

Angelo Veronese, Laura Lupini, Jessica Consiglio, Rosa Visone, Manuela Ferracin, Francesca Fornari, Nicola Zanesi, Hansjuerg Alder, Gemma D'Elia, Laura Gramantieri, Luigi Bolondi, Giovanni Lanza, Patrizia Querzoli, Adriano Angioni, Carlo M. Croce, Massimo Negrini

Research output: Contribution to journalArticlepeer-review


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 ∼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.

Original languageEnglish
Pages (from-to)3140-3149
Number of pages10
JournalCancer Research
Issue number8
Publication statusPublished - Apr 15 2010

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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