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

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Olive, V; Sabio, E; Bennett, MJ; De Jong, CS; Biton, A; McGann, JC; Greaney, SK; Sodir, NM; Zhou, AY; Balakrishnan, A; ...Date
2013-10-15Source Title
eLifePublisher
ELIFE SCIENCES PUBLICATIONS LTDUniversity of Melbourne Author/s
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School of Mathematics and StatisticsMetadata
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Olive, V., Sabio, E., Bennett, M. J., De Jong, C. S., Biton, A., McGann, J. C., Greaney, S. K., Sodir, N. M., Zhou, A. Y., Balakrishnan, A., Foth, M., Luftig, M. A., Goga, A., Speed, T. P., Xuan, Z., Evan, G. I., Wan, Y., Minella, A. C. & He, L. (2013). A component of the mir-17-92 polycistronic oncomir promotes oncogene-dependent apoptosis. ELIFE, 2 (2), https://doi.org/10.7554/eLife.00822.Access Status
Open AccessAbstract
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.
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