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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 15, 2013
- Source ID
- 10.7554/elife.00822
Entities
People
- Alex C Minella
- Alicia Y Zhou
- Andrei Goga
- Anne Biton
- Asha Balakrishnan
- Caitlin S De Jong
- Erich Sabio
- Gerard I. Evan
- James C Mcgann
- Lin He
- Margaux J Bennett
- Micah A Luftig
- Mona Foth
- Nicole M Sodir
- Samantha K Greaney
- Terence P. Speed
- Virginie Olive
- Ying Wan
- Zhenyu Xuan
Organizations
- American Cancer Society
- Army Medical University
- Duke University
- Istituto Superiore di Sanità
- Leukemia & Lymphoma Society
- National Cancer Institute
- National Heart, Lung, and Blood Institute
- National Institutes of Health
- Northwestern University
- Statistics New Zealand
- Tobacco-Related Disease Research Program
- United States Department of Defense
- University of California
- University of Cambridge
- University of Texas at Dallas