UPF1 promotes chemoresistance to oxaliplatin through regulation of TOP2A activity and maintenance of stemness in colorectal cancer
Abstract 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 overa...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2021-05-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-021-03798-2 |
| _version_ | 1818671306612146176 |
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| author | Congcong Zhu Long Zhang Senlin Zhao Weixing Dai Yun Xu Yuqin Zhang Hongtu Zheng Weiqi Sheng Ye Xu |
| author_facet | Congcong Zhu Long Zhang Senlin Zhao Weixing Dai Yun Xu Yuqin Zhang Hongtu Zheng Weiqi Sheng Ye Xu |
| author_sort | Congcong Zhu |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-17T07:21:55Z |
| format | Article |
| id | doaj.art-ecaa7602f3f24984b4f83f5c0b621a1b |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-17T07:21:55Z |
| publishDate | 2021-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-ecaa7602f3f24984b4f83f5c0b621a1b2022-12-21T21:58:44ZengNature Publishing GroupCell Death and Disease2041-48892021-05-0112611510.1038/s41419-021-03798-2UPF1 promotes chemoresistance to oxaliplatin through regulation of TOP2A activity and maintenance of stemness in colorectal cancerCongcong Zhu0Long Zhang1Senlin Zhao2Weixing Dai3Yun Xu4Yuqin Zhang5Hongtu Zheng6Weiqi Sheng7Ye Xu8Department of Colorectal Surgery, Fudan University Shanghai Cancer CenterDepartment of Colorectal Surgery, Fudan University Shanghai Cancer CenterDepartment of Colorectal Surgery, Fudan University Shanghai Cancer CenterDepartment of Colorectal Surgery, Fudan University Shanghai Cancer CenterDepartment of Colorectal Surgery, Fudan University Shanghai Cancer CenterDepartment of Colorectal Surgery, Fudan University Shanghai Cancer CenterDepartment of Colorectal Surgery, Fudan University Shanghai Cancer CenterDepartment of Oncology, Shanghai Medical College, Fudan UniversityDepartment of Colorectal Surgery, Fudan University Shanghai Cancer CenterAbstract 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.https://doi.org/10.1038/s41419-021-03798-2 |
| spellingShingle | Congcong Zhu Long Zhang Senlin Zhao Weixing Dai Yun Xu Yuqin Zhang Hongtu Zheng Weiqi Sheng Ye Xu UPF1 promotes chemoresistance to oxaliplatin through regulation of TOP2A activity and maintenance of stemness in colorectal cancer Cell Death and Disease |
| 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 |
| url | https://doi.org/10.1038/s41419-021-03798-2 |
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