Journal article

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

Virginie Olive, Erich Sabio, Margaux J Bennett, Caitlin S De Jong, Anne Biton, James C McGann, Samantha K Greaney, Nicole M Sodir, Alicia Y Zhou, Asha Balakrishnan, Mona Foth, Micah A Luftig, Andrei Goga, Terence P Speed, Zhenyu Xuan, Gerard I Evan, Ying Wan, Alex C Minella, Lin He

ELIFE | ELIFE SCIENCES PUBLICATIONS LTD | Published : 2013

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..

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University of Melbourne Researchers

Grants

Awarded by American Cancer Society


Awarded by National Cancer Institute


Awarded by Leukemia and Lymphoma Society LLS


Awarded by National Instititute of Health


Awarded by National Heart, Lung and Blood Institute


Awarded by Alex C Minella US Department of Defense


Awarded by Cancer Research UK


Awarded by NATIONAL CANCER INSTITUTE


Awarded by NATIONAL HEART, LUNG, AND BLOOD INSTITUTE


Funding Acknowledgements

American Cancer Society 123339-RSG-12-265-01-RMC Lin HeNational Cancer Institute R00 CA126186 Lin HeThe Leukemia and Lymphoma Society LLS, 3423-13 Virginie OliveNational Instititute of Health F31 CA165825-02 Erich SabioNational Cancer Institute R01 CA139067 Lin HeNational Cancer Institute 1R21CA175560-01 Lin HeNational Institute of Health R01HL098608 Alex C MinellaNational Heart, Lung and Blood Institute R01HL098608 Alex C MinellaUS Department of Defense W81XWH-12-1-0272 Andrei GogaNational Institutes of Health 5R01CA170447 Andrei GogaThe Leukemia and Lymphoma Society LLS, 1531 Andrei Goga