A component of the mir-17-92 polycistronic oncomir promotes oncogene-dependent apoptosis

Virginie Olive, Erich Sabio, Margaux J. Bennett, Caitlin S. De Jong, Anne Biton, James C. McGann, Samantha K. Greaney, Nicole M. Sodir, Alicia Y. Zhou, Asha Balakrishnan, Mona Foth, Micah A. Luftig, Andrei Goga, Terence P. Speed, Zhenyu Xuan, Gerard I. Evan, Ying Wan, Alex C. Minella, Lin He

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

mir-17-92, a potent polycistronic oncomir, encodes six mature miRNAs with complex modes of interactions. In the Eμ-myc Burkitt's lymphoma model, mir-17-92 exhibits potent oncogenic activity by repressing c-Myc-induced apoptosis, primarily through its miR-19 components. Surprisingly, mir-17-92 also encodes the miR-92 component that negatively regulates its oncogenic cooperation with c-Myc. This miR-92 effect is, at least in part, mediated by its direct repression of Fbw7, which promotes the proteosomal degradation of c-Myc. Thus, overexpressing miR-92 leads to aberrant c-Myc increase, imposing a strong coupling between excessive proliferation and p53-dependent apoptosis. Interestingly, miR-92 antagonizes the oncogenic miR-19 miRNAs; and such functional interaction coordinates proliferation and apoptosis during c-Myc-induced oncogenesis. This miR-19:miR-92 antagonism is disrupted in B-lymphoma cells that favor a greater increase of miR-19 over miR-92. Altogether, we suggest a new paradigm whereby the unique gene structure of a polycistronic oncomir confers an intricate balance between oncogene and tumor suppressor crosstalk.

Original languageEnglish (US)
Article numbere00822
JournaleLife
Volume2013
Issue number2
DOIs
StatePublished - Oct 15 2013

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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