Effect of knockdown OFD1 on gene expression in pancreatic cancer cells
PARP inhibitors (PARPi) have demonstrated efficacy in treating human cancers with BRCA1 or BRCA2 gene mutations, which are present in only a small portion of breast, ovarian, prostate, and pancreatic cancers. In this study, we discovered that OFD1 is highly expressed in pancreatic cancer and is associated with a poor prognosis. Through screening an FDA-approved drug library, we found that OFD1 knockdown synergizes most effectively with PARPi for the treatment of pancreatic cancer cells. To explore the mechanism of OFD1 knockdown and PARP inhibitor-induced synthetic lethality, we knocked down OFD1 in three pancreatic cancer cell lines and performed RNA sequencing analysis of the whole genome to investigate the mechanisms underlying OFD1 inhibition and PARP inhibitor-induced synthetic lethality. In summary, our research will provide insights into the role of OFD1 in pancreatic cancer by revealing changes in the whole-genome expression profile and the underlying mechanisms. Overall design: RNA sequencing analysis was performed on wild-type pancreatic cancer cell lines (MIA PaCa-2, PANC-1, PaTu 8988T) and their knockdown derivatives (shOFD1) at 0 and 3 days following doxycycline-induced knockdown