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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Veronese A,Lupini L,Consiglio J,Visone R,Ferracin M,Fornari F,Zanesi N,Alder H,D'Elia G,Gramantieri L,Bolondi L,Lanza G,Querzoli P,Angioni A,Croce CM,Negrini Mdoi
10.1158/0008-5472.CAN-09-4456subject
Has Abstractpub_date
2010-04-15 00:00:00pages
3140-9issue
8eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-09-4456journal_volume
70pub_type
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