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UPF1 promotes chemoresistance to oxaliplatin through regulation of TOP2A activity and maintenance of stemness in colorectal cancer
- Source :
- Cell Death and Disease, Vol 12, Iss 6, Pp 1-15 (2021), Cell Death & Disease
- Publication Year :
- 2021
- Publisher :
- Nature Publishing Group, 2021.
-
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.
- Subjects :
- 0301 basic medicine
Cancer Research
Poor prognosis
Colorectal cancer
Immunology
medicine.disease_cause
Article
Prognostic markers
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Downregulation and upregulation
In vivo
medicine
Humans
Multiple tumors
Poly-ADP-Ribose Binding Proteins
neoplasms
Zinc finger
QH573-671
business.industry
Oncogenes
Cell Biology
Middle Aged
medicine.disease
digestive system diseases
Oxaliplatin
DNA Topoisomerases, Type II
030104 developmental biology
030220 oncology & carcinogenesis
Trans-Activators
Cancer research
Colorectal Neoplasms
Carcinogenesis
business
Cytology
RNA Helicases
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 20414889
- Volume :
- 12
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Cell Death and Disease
- Accession number :
- edsair.doi.dedup.....3062c7dcfc1cad90fdf1e74468b37391