Oncogenic Role of miR-483-3p at the IGF2/483 Locus
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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.
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In HepG2 cells, miR-483 has oncogenic potential through inhibition of apoptotic regulatory genes PUMA/BBC3.
“In the hepatocarcinoma cell line HepG2, observational studies revealed the oncogenic potential of miR-483 through inhibition of apoptotic regulatory genes PUMA/BBC3 (201).”
From Adrenocortical carcinoma (2014) · cites this paper as [201]
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- Authors
- 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, C. M., & Negrini, M.
- Affiliations
- University of Ferrara (IT)
- Authors' Affiliations: 1Dipartimento di Medicina Sperimentale e Diagnostica, Università di Ferrara, Ferrara, Italy; 2Dipartimento di Medicina Interna e Gastroenterologia, Università di Bologna, Bologna, Italy; 3Department of Molecular Virology, Immunology, and Medical Genetics, Ohio State University, Columbus, Ohio; and 4Ospedale Bambin Gesù, IRCCS, Struttura Semplice di Citogenetica e Genetica Molecolare, Rome, Italy
- Corresponding author
- Negrini, Massimo
- ORCID
- Venue
- Cancer Research
- Published
- 2010-04-14
- Volume
- 70
- Issue
- 8
- Pages
- 3140-3149
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC4303586
- OpenAlex
- W2125417601
- Cited by
- 210
- References
- 36
- Citations by year
- 2025: 6 · 2024: 10 · 2023: 10 · 2022: 7 · 2021: 13 · 2020: 7 · 2019: 18 · 2018: 15 · 2017: 11 · 2016: 12 · 2015: 14 · 2014: 15 · 2013: 27 · 2012: 19
- FWCI
- 7.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
- Funders
- National Cancer Institute (P30CA016058)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- miR-483-3p, insulin-like growth factor II, oncogenic microRNA, apoptosis, Wilms tumor, colon cancer, breast cancer, liver cancer, HepG2 cells, cancer therapy targets
- MeSH terms
- Animals, Humans, Insulin-Like Growth Factor II, Introns, Wilms Tumor, Oligonucleotides, Oncogenes, RNA, Messenger, Mice, SCID, Apoptosis, RNA, Small Interfering, MicroRNAs, Cell Line, Tumor, Mice, Hep G2 Cells
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