title: A component of the mir-17-92 polycistronic oncomir promotes oncogene-dependent apoptosis.
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.
authors.affiliation: Department of Molecular and Cell Biology , University of California, Berkeley , Berkeley , United States.
authors.forename: Virginie
authors.initials: V
authors.lastname: Olive
authors.forename: Erich
authors.initials: E
authors.lastname: Sabio
authors.forename: Margaux J
authors.initials: MJ
authors.lastname: Bennett
authors.forename: Caitlin S
authors.initials: CS
authors.lastname: De Jong
authors.forename: Anne
authors.initials: A
authors.lastname: Biton
authors.forename: James C
authors.initials: JC
authors.lastname: McGann
authors.forename: Samantha K
authors.initials: SK
authors.lastname: Greaney
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Sodir
authors.forename: Alicia Y
authors.initials: AY
authors.lastname: Zhou
authors.forename: Asha
authors.initials: A
authors.lastname: Balakrishnan
authors.forename: Mona
authors.initials: M
authors.lastname: Foth
authors.forename: Micah A
authors.initials: MA
authors.lastname: Luftig
authors.forename: Andrei
authors.initials: A
authors.lastname: Goga
authors.forename: Terence P
authors.initials: TP
authors.lastname: Speed
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Xuan
authors.forename: Gerard I
authors.initials: GI
authors.lastname: Evan
authors.forename: Ying
authors.initials: Y
authors.lastname: Wan
authors.forename: Alex C
authors.initials: AC
authors.lastname: Minella
authors.forename: Lin
authors.initials: L
authors.lastname: He
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D009857:Oncogenes
chemical_list: C575895:MIRN17-92 microRNA, mouse; D035683:MicroRNAs
keywords: Eμ-myc lymphoma; Mouse; apoptosis; c-Myc; microRNAs; p53