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

Published online

Journal Article

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. DOI:http://dx.doi.org/10.7554/eLife.00822.001.

Full Text

Duke Authors

Cited Authors

  • Olive, V; Sabio, E; Bennett, MJ; De Jong, CS; Biton, A; McGann, JC; Greaney, SK; Sodir, NM; Zhou, AY; Balakrishnan, A; Foth, M; Luftig, MA; Goga, A; Speed, TP; Xuan, Z; Evan, GI; Wan, Y; Minella, AC; He, L

Published Date

  • October 15, 2013

Published In

Volume / Issue

  • 2 /

Start / End Page

  • e00822 -

PubMed ID

  • 24137534

Pubmed Central ID

  • 24137534

International Standard Serial Number (ISSN)

  • 2050-084X

Digital Object Identifier (DOI)

  • 10.7554/eLife.00822

Language

  • eng

Conference Location

  • England