PAFAH1B3 is a KLF9 target gene and promotes proliferation and metastasis in pancreatic cancer

Abstract

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies. Unlimited proliferation, invasion and migration of pancreatic cancer cells are the fundamental causes of death in PDAC. Previous studies by our group have shown that KLF9 inhibits the proliferation, invasion and migration of pancreatic cancer cells. However, the mechanisms are not fully understood. In this study, we found that platelet-activating factor acetylhydrolase IB3 (PAFAH1B3) was highly expressed in pancreatic cancer tissues and cells. In vitro and in vivo studies showed that overexpression of PAFAH1B3 promoted the proliferation and invasion of pancreatic cancer cells, while downregulation of PAFAH1B3 inhibited the proliferation and invasion of pancreatic cancer cells. Mechanistically, KLF9 expression was negatively correlated with PAFAH1B3 expression in pancreatic cancer tissues and cells. Western blotting showed that KLF9 negatively regulated the expression of PAFAH1B3 in pancreatic cancer tissues and cells. Rescue experiments showed that overexpression of PAFAH1B3 could partially rescue the reduction in pancreatic cancer cell proliferation, invasion and migration induced by KLF9 overexpression. Finally, chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were carried out, and the results showed that KLF9 directly bound to the promoter of PAFAH1B3 and inhibited its transcriptional activity. In conclusion, our study indicated that KLF9 can inhibit the proliferation, invasion, migration and metastasis of pancreatic cancer cells by inhibiting PAFAH1B3.