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Activating and sustaining c-Myc by depletion of miR-144/451 gene locus contributes to B-lymphomagenesis
Hyper activity of protooncogene c-Myc is one of the hallmarks of highly aggressive lymphomas. However, the mechanism of how c-Myc is subjected to activation and amplification is still not well defined. In this study, we use gene knockout strategy to show that targeted depletion of a well-conserved m...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168470/ https://www.ncbi.nlm.nih.gov/pubmed/29284789 http://dx.doi.org/10.1038/s41388-017-0055-5 |
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author | Ding, Lan Zhang, Yanqing Han, Lingling Fu, Lei Mei, Xia Wang, Jijun Itkow, Jacobi Elabid, Afaf Elabid Ibrahim Pang, Lei Yu, Duonan |
author_facet | Ding, Lan Zhang, Yanqing Han, Lingling Fu, Lei Mei, Xia Wang, Jijun Itkow, Jacobi Elabid, Afaf Elabid Ibrahim Pang, Lei Yu, Duonan |
author_sort | Ding, Lan |
collection | PubMed |
description | Hyper activity of protooncogene c-Myc is one of the hallmarks of highly aggressive lymphomas. However, the mechanism of how c-Myc is subjected to activation and amplification is still not well defined. In this study, we use gene knockout strategy to show that targeted depletion of a well-conserved microRNA gene locus miR-144/451 initiates tumorigenesis including B-lymphoma development in aged mice. This is due, at least in part, to the direct activation of the c-Myc gene by loss of miR-144/451 expression in hematopoietic cells. Moreover, oncoprotein c-Myc inversely regulates miR-144/451 expression by directly binding to the miR-144/451 promoter region, forming a miRNA-Myc positive feedback loop to safeguard the high level of c-Myc in B-lymphocytes. We also demonstrate that this miRNA-Myc crosstalk is disrupted in human diffuse large B-cell lymphomas with aberrant c-Myc expression. Therefore, our findings provide strong evidence, for the first time, that deficiency of miR-144/451 expression may play a bona fide role in derepression of silenced c-Myc, which contributes to tumor development including B-lymphomagenesis. |
format | Online Article Text |
id | pubmed-6168470 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61684702018-10-09 Activating and sustaining c-Myc by depletion of miR-144/451 gene locus contributes to B-lymphomagenesis Ding, Lan Zhang, Yanqing Han, Lingling Fu, Lei Mei, Xia Wang, Jijun Itkow, Jacobi Elabid, Afaf Elabid Ibrahim Pang, Lei Yu, Duonan Oncogene Article Hyper activity of protooncogene c-Myc is one of the hallmarks of highly aggressive lymphomas. However, the mechanism of how c-Myc is subjected to activation and amplification is still not well defined. In this study, we use gene knockout strategy to show that targeted depletion of a well-conserved microRNA gene locus miR-144/451 initiates tumorigenesis including B-lymphoma development in aged mice. This is due, at least in part, to the direct activation of the c-Myc gene by loss of miR-144/451 expression in hematopoietic cells. Moreover, oncoprotein c-Myc inversely regulates miR-144/451 expression by directly binding to the miR-144/451 promoter region, forming a miRNA-Myc positive feedback loop to safeguard the high level of c-Myc in B-lymphocytes. We also demonstrate that this miRNA-Myc crosstalk is disrupted in human diffuse large B-cell lymphomas with aberrant c-Myc expression. Therefore, our findings provide strong evidence, for the first time, that deficiency of miR-144/451 expression may play a bona fide role in derepression of silenced c-Myc, which contributes to tumor development including B-lymphomagenesis. Nature Publishing Group UK 2017-12-29 2018 /pmc/articles/PMC6168470/ /pubmed/29284789 http://dx.doi.org/10.1038/s41388-017-0055-5 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. If you remix, transform, or build upon this article or a part thereof, you must distribute your contributions under the same license as the original. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/. |
spellingShingle | Article Ding, Lan Zhang, Yanqing Han, Lingling Fu, Lei Mei, Xia Wang, Jijun Itkow, Jacobi Elabid, Afaf Elabid Ibrahim Pang, Lei Yu, Duonan Activating and sustaining c-Myc by depletion of miR-144/451 gene locus contributes to B-lymphomagenesis |
title | Activating and sustaining c-Myc by depletion of miR-144/451 gene locus contributes to B-lymphomagenesis |
title_full | Activating and sustaining c-Myc by depletion of miR-144/451 gene locus contributes to B-lymphomagenesis |
title_fullStr | Activating and sustaining c-Myc by depletion of miR-144/451 gene locus contributes to B-lymphomagenesis |
title_full_unstemmed | Activating and sustaining c-Myc by depletion of miR-144/451 gene locus contributes to B-lymphomagenesis |
title_short | Activating and sustaining c-Myc by depletion of miR-144/451 gene locus contributes to B-lymphomagenesis |
title_sort | activating and sustaining c-myc by depletion of mir-144/451 gene locus contributes to b-lymphomagenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168470/ https://www.ncbi.nlm.nih.gov/pubmed/29284789 http://dx.doi.org/10.1038/s41388-017-0055-5 |
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