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MYC is a positive regulator of choline metabolism and impedes mitophagy-dependent necroptosis in diffuse large B-cell lymphoma
The activation of oncogenes can reprogram tumor cell metabolism. Here, in diffuse large B-cell lymphoma (DLBCL), serum metabolomic analysis revealed that oncogenic MYC could induce aberrant choline metabolism by transcriptionally activating the key enzyme phosphate cytidylyltransferase 1 choline-α (...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549253/ https://www.ncbi.nlm.nih.gov/pubmed/28686226 http://dx.doi.org/10.1038/bcj.2017.61 |
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author | Xiong, J Wang, L Fei, X-C Jiang, X-F Zheng, Z Zhao, Y Wang, C-F Li, B Chen, S-J Janin, A Gale, R P Zhao, W-L |
author_facet | Xiong, J Wang, L Fei, X-C Jiang, X-F Zheng, Z Zhao, Y Wang, C-F Li, B Chen, S-J Janin, A Gale, R P Zhao, W-L |
author_sort | Xiong, J |
collection | PubMed |
description | The activation of oncogenes can reprogram tumor cell metabolism. Here, in diffuse large B-cell lymphoma (DLBCL), serum metabolomic analysis revealed that oncogenic MYC could induce aberrant choline metabolism by transcriptionally activating the key enzyme phosphate cytidylyltransferase 1 choline-α (PCYT1A). In B-lymphoma cells, as a consequence of PCYT1A upregulation, MYC impeded lymphoma cells undergo a mitophagy-dependent necroptosis. In DLBCL patients, overexpression of PCYT1A was in parallel with an increase in tumor MYC, as well as a decrease in serum choline metabolite phosphatidylcholine levels and an International Prognostic Index, indicating intermediate–high or high risk. Both in vitro and in vivo, lipid-lowering alkaloid berberine (BBR) exhibited an anti-lymphoma activity through inhibiting MYC-driven downstream PCYT1A expression and inducing mitophagy-dependent necroptosis. Collectively, PCYT1A was upregulated by MYC, which resulted in the induction of aberrant choline metabolism and the inhibition of B-lymphoma cell necroptosis. Referred as a biomarker for DLBCL progression, PCYT1A can be targeted by BBR, providing a potential lipid-modifying strategy in treating MYC-High lymphoma. |
format | Online Article Text |
id | pubmed-5549253 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-55492532017-08-11 MYC is a positive regulator of choline metabolism and impedes mitophagy-dependent necroptosis in diffuse large B-cell lymphoma Xiong, J Wang, L Fei, X-C Jiang, X-F Zheng, Z Zhao, Y Wang, C-F Li, B Chen, S-J Janin, A Gale, R P Zhao, W-L Blood Cancer J Original Article The activation of oncogenes can reprogram tumor cell metabolism. Here, in diffuse large B-cell lymphoma (DLBCL), serum metabolomic analysis revealed that oncogenic MYC could induce aberrant choline metabolism by transcriptionally activating the key enzyme phosphate cytidylyltransferase 1 choline-α (PCYT1A). In B-lymphoma cells, as a consequence of PCYT1A upregulation, MYC impeded lymphoma cells undergo a mitophagy-dependent necroptosis. In DLBCL patients, overexpression of PCYT1A was in parallel with an increase in tumor MYC, as well as a decrease in serum choline metabolite phosphatidylcholine levels and an International Prognostic Index, indicating intermediate–high or high risk. Both in vitro and in vivo, lipid-lowering alkaloid berberine (BBR) exhibited an anti-lymphoma activity through inhibiting MYC-driven downstream PCYT1A expression and inducing mitophagy-dependent necroptosis. Collectively, PCYT1A was upregulated by MYC, which resulted in the induction of aberrant choline metabolism and the inhibition of B-lymphoma cell necroptosis. Referred as a biomarker for DLBCL progression, PCYT1A can be targeted by BBR, providing a potential lipid-modifying strategy in treating MYC-High lymphoma. Nature Publishing Group 2017-07 2017-07-07 /pmc/articles/PMC5549253/ /pubmed/28686226 http://dx.doi.org/10.1038/bcj.2017.61 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | Original Article Xiong, J Wang, L Fei, X-C Jiang, X-F Zheng, Z Zhao, Y Wang, C-F Li, B Chen, S-J Janin, A Gale, R P Zhao, W-L MYC is a positive regulator of choline metabolism and impedes mitophagy-dependent necroptosis in diffuse large B-cell lymphoma |
title | MYC is a positive regulator of choline metabolism and impedes mitophagy-dependent necroptosis in diffuse large B-cell lymphoma |
title_full | MYC is a positive regulator of choline metabolism and impedes mitophagy-dependent necroptosis in diffuse large B-cell lymphoma |
title_fullStr | MYC is a positive regulator of choline metabolism and impedes mitophagy-dependent necroptosis in diffuse large B-cell lymphoma |
title_full_unstemmed | MYC is a positive regulator of choline metabolism and impedes mitophagy-dependent necroptosis in diffuse large B-cell lymphoma |
title_short | MYC is a positive regulator of choline metabolism and impedes mitophagy-dependent necroptosis in diffuse large B-cell lymphoma |
title_sort | myc is a positive regulator of choline metabolism and impedes mitophagy-dependent necroptosis in diffuse large b-cell lymphoma |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549253/ https://www.ncbi.nlm.nih.gov/pubmed/28686226 http://dx.doi.org/10.1038/bcj.2017.61 |
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