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Oncogenic role of miR-483-3p at the IGF2/483 locus

Angelo Veronese1, Laura Lupini, Jessica Consiglio

  • 1Dipartimento di Medicina Sperimentale e Diagnostica, Università di Ferrara, Ferrara, Italy.

Cancer Research
|April 15, 2010
PubMed

Insights

MicroRNA miR-483-3p is overexpressed in Wilms' tumors and other cancers, acting as an oncogene. Inhibiting miR-483-3p suppressed tumor growth, suggesting it as a therapeutic target.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • hsa-mir-483 is located within intron 2 of the IGF2 locus.
  • MicroRNA (miRNA) miR-483-3p is frequently overexpressed in Wilms' tumors and other human cancers.
  • Potential coregulation of miR-483-3p with IGF2 mRNA has been observed.

Purpose of the Study:

  • To investigate the oncogenic role of miR-483-3p.
  • To determine if miR-483-3p acts as an autonomous oncogene or cooperates with IGF2.
  • To explore miR-483-3p as a potential therapeutic target in cancer.

Main Methods:

  • Utilized anti-miRNA oligonucleotides to inhibit miR-483-3p in cancer cells.
  • Assessed the effect of inhibition on tumorigenicity and IGF2 mRNA levels.
  • Investigated the impact of miR-483-3p on apoptosis by examining BBC3/PUMA modulation.

Main Results:

  • Inhibition of miR-483-3p suppressed tumorigenicity of HepG2 cells without affecting IGF2 mRNA.
  • Inhibition of IGF2 alone did not elicit an antitumor effect.
  • miR-483-3p was found to modulate the proapoptotic protein BBC3/PUMA, protecting cells from apoptosis.

Conclusions:

  • miR-483-3p functions as an antiapoptotic oncogene in various human cancers.
  • miR-483-3p acts as an autonomous oncogene, independent of IGF2.
  • miR-483-3p represents a novel and significant therapeutic target for anticancer strategies.

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