title: 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.affiliation: Dipartimento di Medicina Sperimentale e Diagnostica, Università di Ferrara, Ferrara, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Veronese
authors.forename: Laura
authors.initials: L
authors.lastname: Lupini
authors.forename: Jessica
authors.initials: J
authors.lastname: Consiglio
authors.forename: Rosa
authors.initials: R
authors.lastname: Visone
authors.forename: Manuela
authors.initials: M
authors.lastname: Ferracin
authors.forename: Francesca
authors.initials: F
authors.lastname: Fornari
authors.forename: Nicola
authors.initials: N
authors.lastname: Zanesi
authors.forename: Hansjuerg
authors.initials: H
authors.lastname: Alder
authors.forename: Gemma
authors.initials: G
authors.lastname: D'Elia
authors.forename: Laura
authors.initials: L
authors.lastname: Gramantieri
authors.forename: Luigi
authors.initials: L
authors.lastname: Bolondi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lanza
authors.forename: Patrizia
authors.initials: P
authors.lastname: Querzoli
authors.forename: Adriano
authors.initials: A
authors.lastname: Angioni
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
authors.forename: Massimo
authors.initials: M
authors.lastname: Negrini
mesh_terms: 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
chemical_list: 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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