A component of the mir-17-92 polycistronic oncomir promotes oncogene-dependent apoptosis
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 e...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2013-10-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/00822 |
| _version_ | 1811199601592500224 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Virginie Olive |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T01:50:16Z |
| format | Article |
| id | doaj.art-40ffbb1f349b467aad6234770c960db3 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:50:16Z |
| publishDate | 2013-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-40ffbb1f349b467aad6234770c960db32022-12-22T03:52:57ZengeLife Sciences Publications LtdeLife2050-084X2013-10-01210.7554/eLife.00822A component of the mir-17-92 polycistronic oncomir promotes oncogene-dependent apoptosisVirginie Olive0Erich Sabio1Margaux J Bennett2Caitlin S De Jong3Anne Biton4James C McGann5Samantha K Greaney6Nicole M Sodir7Alicia Y Zhou8Asha Balakrishnan9Mona Foth10Micah A Luftig11Andrei Goga12Terence P Speed13Zhenyu Xuan14Gerard I Evan15Ying Wan16Alex C Minella17Lin He18Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDepartment of Statistics, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDepartment of Biochemistry, University of Cambridge, Cambridge, United KingdomDepartment of Cell and Tissue Biology, University of California, San Francisco, San Francisco, United StatesDepartment of Cell and Tissue Biology, University of California, San Francisco, San Francisco, United StatesDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular Genetics and Microbiology, Duke University, Durham, United StatesDepartment of Cell and Tissue Biology, University of California, San Francisco, San Francisco, United StatesDepartment of Statistics, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, Center for Systems Biology, University of Texas at Dallas, Dallas, United StatesDepartment of Biochemistry, University of Cambridge, Cambridge, United KingdomDepartment of Medicine, The Third Military Medical University, Chongqing, ChinaDriskill Graduate Program, Department of Medicine, Hematology and Oncology Division, Northwestern University Feinberg School of Medicine, Chicago, United StatesDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United Statesmir-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.https://elifesciences.org/articles/00822microRNAc-MycEμ-myc lymphomaapoptosisp53 |
| spellingShingle | 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 A component of the mir-17-92 polycistronic oncomir promotes oncogene-dependent apoptosis eLife microRNA c-Myc Eμ-myc lymphoma apoptosis p53 |
| title | A component of the mir-17-92 polycistronic oncomir promotes oncogene-dependent apoptosis |
| title_full | A component of the mir-17-92 polycistronic oncomir promotes oncogene-dependent apoptosis |
| title_fullStr | A component of the mir-17-92 polycistronic oncomir promotes oncogene-dependent apoptosis |
| title_full_unstemmed | A component of the mir-17-92 polycistronic oncomir promotes oncogene-dependent apoptosis |
| title_short | A component of the mir-17-92 polycistronic oncomir promotes oncogene-dependent apoptosis |
| title_sort | component of the mir 17 92 polycistronic oncomir promotes oncogene dependent apoptosis |
| topic | microRNA c-Myc Eμ-myc lymphoma apoptosis p53 |
| url | https://elifesciences.org/articles/00822 |
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