The hsa-mir-483 is located within intron 2 of the IGF2 locus. We found that the mature microRNA (miRNA) miR-483-3p is over-expressed in 100% of Wilms' tumors. In addition, colon, breast and liver cancers exhibit high or even extremely high levels of miR-483-3p in about 30% of the cases. A co-regulation 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-microRNA oligonucleotide (AMO) against miR-483-3p could inhibit the miRNA without affecting IGF2 mRNA and it could suppress tumorigenicity of HepG2 cells, a cell line that over-expresses miR-483-3p and IGF2. Conversely, no anti-tumor effect was elicited by inhibition of IGF2. The oncogenic mechanism of miR-483-3p was at least partially clarified by the finding that it can modulate the pro-apoptotic protein BBC3/PUMA and miR-483-3p enforced expression could protect cells from apoptosis. Our results indicate that miR-483-3p can function as an anti-apoptotic oncogene in various human cancers and reveal a new potentially important target for anti-cancer therapy.
Oncogenic role of miR-483-3p at the IGF2/483 locus
VERONESE, Angelo;LUPINI, Laura;FERRACIN, Manuela;LANZA, Giovanni;QUERZOLI, Patrizia;CROCE, Carlo Maria;NEGRINI, Massimo
2010
Abstract
The hsa-mir-483 is located within intron 2 of the IGF2 locus. We found that the mature microRNA (miRNA) miR-483-3p is over-expressed in 100% of Wilms' tumors. In addition, colon, breast and liver cancers exhibit high or even extremely high levels of miR-483-3p in about 30% of the cases. A co-regulation 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-microRNA oligonucleotide (AMO) against miR-483-3p could inhibit the miRNA without affecting IGF2 mRNA and it could suppress tumorigenicity of HepG2 cells, a cell line that over-expresses miR-483-3p and IGF2. Conversely, no anti-tumor effect was elicited by inhibition of IGF2. The oncogenic mechanism of miR-483-3p was at least partially clarified by the finding that it can modulate the pro-apoptotic protein BBC3/PUMA and miR-483-3p enforced expression could protect cells from apoptosis. Our results indicate that miR-483-3p can function as an anti-apoptotic oncogene in various human cancers and reveal a new potentially important target for anti-cancer therapy.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
