Oncogenic role of miR-483-3p at the IGF2/483 locus.
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.
Veronese
Angelo
A
Dipartimento di Medicina Sperimentale e Diagnostica, Università di Ferrara, Ferrara, Italy.
Lupini
Laura
L
Consiglio
Jessica
J
Visone
Rosa
R
Ferracin
Manuela
M
Fornari
Francesca
F
Zanesi
Nicola
N
Alder
Hansjuerg
H
D'Elia
Gemma
G
Gramantieri
Laura
L
Bolondi
Luigi
L
Lanza
Giovanni
G
Querzoli
Patrizia
P
Angioni
Adriano
A
Croce
Carlo M
CM
Negrini
Massimo
M
D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D056945:Hep G2 Cells; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000378:metabolism*; D007438:Introns; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000378:metabolism*; D009841:Oligonucleotides / Q000737:chemistry; D009857:Oncogenes; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D009396:Wilms Tumor / Q000235:genetics / Q000378:metabolism
C548912:MIRN483 microRNA, human; D035683:MicroRNAs; C548913:Mirn483 microRNA, mouse; D009841:Oligonucleotides; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D007335:Insulin-Like Growth Factor II
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