Genetic inactivation of Peroxiredoxin-I impairs the growth of human pancreatic cancer cells

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with few therapeutic op-tions. The identification of new promising targets is therefore an urgent need. Using available transcriptomic datasets, we first found that Peroxiredoxin-1 gene (PRDX1) expression is signifi-cantly 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 strate-gies, 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.