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Elife. 2013 Oct 15;2:e00822. doi: 10.7554/eLife.00822.

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

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1
Department of Molecular and Cell Biology , University of California, Berkeley , Berkeley , United States.

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

KEYWORDS:

Eμ-myc lymphoma; Mouse; apoptosis; c-Myc; microRNAs; p53

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PMID:
24137534
PMCID:
PMC3796314
DOI:
10.7554/eLife.00822
[Indexed for MEDLINE]
Free PMC Article
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