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TRIM25 regulates oxaliplatin resistance in colorectal cancer by promoting EZH2 stability
Resistance to chemotherapy remains the major cause of treatment failure in patients with colorectal cancer (CRC). Here, we identified TRIM25 as an epigenetic regulator of oxaliplatin (OXA) resistance in CRC. The level of TRIM25 in OXA-resistant patients who experienced recurrence during the follow-u...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106682/ https://www.ncbi.nlm.nih.gov/pubmed/33966039 http://dx.doi.org/10.1038/s41419-021-03734-4 |
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author | Zhou, Sha Peng, Jianhong Xiao, Liuniu Zhou, Caixia Fang, Yujing Ou, Qingjian Qin, Jiayi Liu, Mengzhong Pan, Zhizhong Hou, Zhenlin |
author_facet | Zhou, Sha Peng, Jianhong Xiao, Liuniu Zhou, Caixia Fang, Yujing Ou, Qingjian Qin, Jiayi Liu, Mengzhong Pan, Zhizhong Hou, Zhenlin |
author_sort | Zhou, Sha |
collection | PubMed |
description | Resistance to chemotherapy remains the major cause of treatment failure in patients with colorectal cancer (CRC). Here, we identified TRIM25 as an epigenetic regulator of oxaliplatin (OXA) resistance in CRC. The level of TRIM25 in OXA-resistant patients who experienced recurrence during the follow-up period was significantly higher than in those who had no recurrence. Patients with high expression of TRIM25 had a significantly higher recurrence rate and worse disease-free survival than those with low TRIM25 expression. Downregulation of TRIM25 dramatically inhibited, while overexpression of TRIM25 increased, CRC cell survival after OXA treatment. In addition, TRIM25 promoted the stem cell properties of CRC cells both in vitro and in vivo. Importantly, we demonstrated that TRIM25 inhibited the binding of E3 ubiquitin ligase TRAF6 to EZH2, thus stabilizing and upregulating EZH2, and promoting OXA resistance. Our study contributes to a better understanding of OXA resistance and indicates that inhibitors against TRIM25 might be an excellent strategy for CRC management in clinical practice. |
format | Online Article Text |
id | pubmed-8106682 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-81066822021-05-11 TRIM25 regulates oxaliplatin resistance in colorectal cancer by promoting EZH2 stability Zhou, Sha Peng, Jianhong Xiao, Liuniu Zhou, Caixia Fang, Yujing Ou, Qingjian Qin, Jiayi Liu, Mengzhong Pan, Zhizhong Hou, Zhenlin Cell Death Dis Article Resistance to chemotherapy remains the major cause of treatment failure in patients with colorectal cancer (CRC). Here, we identified TRIM25 as an epigenetic regulator of oxaliplatin (OXA) resistance in CRC. The level of TRIM25 in OXA-resistant patients who experienced recurrence during the follow-up period was significantly higher than in those who had no recurrence. Patients with high expression of TRIM25 had a significantly higher recurrence rate and worse disease-free survival than those with low TRIM25 expression. Downregulation of TRIM25 dramatically inhibited, while overexpression of TRIM25 increased, CRC cell survival after OXA treatment. In addition, TRIM25 promoted the stem cell properties of CRC cells both in vitro and in vivo. Importantly, we demonstrated that TRIM25 inhibited the binding of E3 ubiquitin ligase TRAF6 to EZH2, thus stabilizing and upregulating EZH2, and promoting OXA resistance. Our study contributes to a better understanding of OXA resistance and indicates that inhibitors against TRIM25 might be an excellent strategy for CRC management in clinical practice. Nature Publishing Group UK 2021-05-08 /pmc/articles/PMC8106682/ /pubmed/33966039 http://dx.doi.org/10.1038/s41419-021-03734-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits 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. 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/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Zhou, Sha Peng, Jianhong Xiao, Liuniu Zhou, Caixia Fang, Yujing Ou, Qingjian Qin, Jiayi Liu, Mengzhong Pan, Zhizhong Hou, Zhenlin TRIM25 regulates oxaliplatin resistance in colorectal cancer by promoting EZH2 stability |
title | TRIM25 regulates oxaliplatin resistance in colorectal cancer by promoting EZH2 stability |
title_full | TRIM25 regulates oxaliplatin resistance in colorectal cancer by promoting EZH2 stability |
title_fullStr | TRIM25 regulates oxaliplatin resistance in colorectal cancer by promoting EZH2 stability |
title_full_unstemmed | TRIM25 regulates oxaliplatin resistance in colorectal cancer by promoting EZH2 stability |
title_short | TRIM25 regulates oxaliplatin resistance in colorectal cancer by promoting EZH2 stability |
title_sort | trim25 regulates oxaliplatin resistance in colorectal cancer by promoting ezh2 stability |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106682/ https://www.ncbi.nlm.nih.gov/pubmed/33966039 http://dx.doi.org/10.1038/s41419-021-03734-4 |
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