UPF1 promotes chemoresistance to oxaliplatin through regulation of TOP2A activity and maintenance of stemness in colorectal cancer

UPF1 is proved to dysregulate in multiple tumors and influence carcinogenesis. However, the role of UPF1 in oxaliplatin resistance in colorectal cancer (CRC) remains unknown. In our study, UPF1 is upregulated in CRC in mRNA and protein levels and overexpression of UPF1 predicts a poor overall surviv...

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Autores principales: Zhu, Congcong, Zhang, Long, Zhao, Senlin, Dai, Weixing, Xu, Yun, Zhang, Yuqin, Zheng, Hongtu, Sheng, Weiqi, Xu, Ye
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140095/
https://www.ncbi.nlm.nih.gov/pubmed/34021129
http://dx.doi.org/10.1038/s41419-021-03798-2
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author Zhu, Congcong
Zhang, Long
Zhao, Senlin
Dai, Weixing
Xu, Yun
Zhang, Yuqin
Zheng, Hongtu
Sheng, Weiqi
Xu, Ye
author_facet Zhu, Congcong
Zhang, Long
Zhao, Senlin
Dai, Weixing
Xu, Yun
Zhang, Yuqin
Zheng, Hongtu
Sheng, Weiqi
Xu, Ye
author_sort Zhu, Congcong
collection PubMed
description UPF1 is proved to dysregulate in multiple tumors and influence carcinogenesis. However, the role of UPF1 in oxaliplatin resistance in colorectal cancer (CRC) remains unknown. In our study, UPF1 is upregulated in CRC in mRNA and protein levels and overexpression of UPF1 predicts a poor overall survival (OS) and recurrence-free survival (RFS) in CRC patients and is an independent risk factor for recurrence. UPF1 promotes chemoresistance to oxaliplatin in vitro and in vivo. UPF1-induced oxaliplatin resistance can be associated with interaction between zinc finger of UPF1 and Toprim of TOP2A and increasing phosphorylated TOP2A in a SMG1-dependent manner. Moreover, UPF1 maintains stemness in a TOP2A-dependent manner in CRC. Taken together, UPF1 was overexpressed and predicted a poor prognosis in CRC. UPF1 enhanced chemoresistance to oxaliplatin in CRC, which may result from regulation of TOP2A activity and maintenance of stemness. Our findings could provide a new therapy strategy for chemoresistance to oxaliplatin in CRC patients.
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spelling pubmed-81400952021-06-03 UPF1 promotes chemoresistance to oxaliplatin through regulation of TOP2A activity and maintenance of stemness in colorectal cancer Zhu, Congcong Zhang, Long Zhao, Senlin Dai, Weixing Xu, Yun Zhang, Yuqin Zheng, Hongtu Sheng, Weiqi Xu, Ye Cell Death Dis Article UPF1 is proved to dysregulate in multiple tumors and influence carcinogenesis. However, the role of UPF1 in oxaliplatin resistance in colorectal cancer (CRC) remains unknown. In our study, UPF1 is upregulated in CRC in mRNA and protein levels and overexpression of UPF1 predicts a poor overall survival (OS) and recurrence-free survival (RFS) in CRC patients and is an independent risk factor for recurrence. UPF1 promotes chemoresistance to oxaliplatin in vitro and in vivo. UPF1-induced oxaliplatin resistance can be associated with interaction between zinc finger of UPF1 and Toprim of TOP2A and increasing phosphorylated TOP2A in a SMG1-dependent manner. Moreover, UPF1 maintains stemness in a TOP2A-dependent manner in CRC. Taken together, UPF1 was overexpressed and predicted a poor prognosis in CRC. UPF1 enhanced chemoresistance to oxaliplatin in CRC, which may result from regulation of TOP2A activity and maintenance of stemness. Our findings could provide a new therapy strategy for chemoresistance to oxaliplatin in CRC patients. Nature Publishing Group UK 2021-05-21 /pmc/articles/PMC8140095/ /pubmed/34021129 http://dx.doi.org/10.1038/s41419-021-03798-2 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
Zhu, Congcong
Zhang, Long
Zhao, Senlin
Dai, Weixing
Xu, Yun
Zhang, Yuqin
Zheng, Hongtu
Sheng, Weiqi
Xu, Ye
UPF1 promotes chemoresistance to oxaliplatin through regulation of TOP2A activity and maintenance of stemness in colorectal cancer
title UPF1 promotes chemoresistance to oxaliplatin through regulation of TOP2A activity and maintenance of stemness in colorectal cancer
title_full UPF1 promotes chemoresistance to oxaliplatin through regulation of TOP2A activity and maintenance of stemness in colorectal cancer
title_fullStr UPF1 promotes chemoresistance to oxaliplatin through regulation of TOP2A activity and maintenance of stemness in colorectal cancer
title_full_unstemmed UPF1 promotes chemoresistance to oxaliplatin through regulation of TOP2A activity and maintenance of stemness in colorectal cancer
title_short UPF1 promotes chemoresistance to oxaliplatin through regulation of TOP2A activity and maintenance of stemness in colorectal cancer
title_sort upf1 promotes chemoresistance to oxaliplatin through regulation of top2a activity and maintenance of stemness in colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140095/
https://www.ncbi.nlm.nih.gov/pubmed/34021129
http://dx.doi.org/10.1038/s41419-021-03798-2
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