Dahou, Hajar and Minati, Marie-Albane and Jacquemin, Patrick and Assi, Mohamad (2021) Genetic Inactivation of Peroxiredoxin-I Impairs the Growth of Human Pancreatic Cancer Cells. Antioxidants, 10 (4). p. 570. ISSN 2076-3921
antioxidants-10-00570-v2.pdf - Published Version
Download (3MB)
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with few therapeutic options. The identification of new promising targets is, therefore, an urgent need. Using available transcriptomic datasets, we first found that Peroxiredoxin-1 gene (PRDX1) expression was significantly increased in human pancreatic tumors, but not in the other gastrointestinal cancers; its high expression correlated with shortened patient survival. We confirmed by immunostaining on mouse pancreata the increased Peroxiredoxin-I protein (PRX-I) expression in pancreatic neoplastic lesions and PDAC. To question the role of PRX-I in pancreatic cancer, we genetically inactivated its expression in multiple human PDAC cell lines, using siRNA and CRISPR/Cas9. In both strategies, PRX-I ablation led to reduced survival of PDAC cells. This was mainly due to an increase in the production of reactive oxygen species (ROS), accumulation of oxidative DNA damage (i.e., 8-oxoguanine), and cell cycle blockade at G2/M. Finally, we found that PRX-I ablation disrupts the autophagic flux in PDAC cells, which is essential for their survival. This proof-of-concept study supports a pro-oncogenic role for PRX-I in PDAC.
Item Type: | Article |
---|---|
Subjects: | Oalibrary Press > Agricultural and Food Science |
Depositing User: | Managing Editor |
Date Deposited: | 10 Jul 2023 04:33 |
Last Modified: | 12 Oct 2023 06:08 |
URI: | http://asian.go4publish.com/id/eprint/2483 |