TY - JOUR TI - A component of the mir-17-92 polycistronic oncomir promotes oncogene-dependent apoptosis AU - Olive, Virginie AU - Sabio, Erich AU - Bennett, Margaux J AU - De Jong, Caitlin S AU - Biton, Anne AU - McGann, James C AU - Greaney, Samantha K AU - Sodir, Nicole M AU - Zhou, Alicia Y AU - Balakrishnan, Asha AU - Foth, Mona AU - Luftig, Micah A AU - Goga, Andrei AU - Speed, Terence P AU - Xuan, Zhenyu AU - Evan, Gerard I AU - Wan, Ying AU - Minella, Alex C AU - He, Lin A2 - Dang, Chi Van VL - 2 PY - 2013 DA - 2013/10/15 SP - e00822 C1 - eLife 2013;2:e00822 DO - 10.7554/eLife.00822 UR - https://doi.org/10.7554/eLife.00822 AB - 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. KW - microRNA KW - c-Myc KW - Eμ-myc lymphoma KW - apoptosis KW - p53 JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -