TNFRSF9 Inhibits Pancreatic Cancer Progression by Regulating PAX6-Mediated Cell Proliferation, Migration, and Apoptosis

Objective: This study aimed to explore the function of TNF receptor superfamily member 9 (TNFRSF9) in pancreatic ductal adenocarcinoma (PDA) by investigating its expression levels and functional implications in PDA cells. Methods: TNFRSF9 expression was evaluated in PDA patients, and TNFRSF9 levels were manipulated in PDA cells to assess its effects on cell proliferation, migration, and apoptosis. The downstream target gene PAX6 was also examined. In vivo, studies in nude mice were performed to analyze the impact of TNFRSF9 overexpression on tumor growth. Results: Analysis revealed decreased TNFRSF9 expression in PDA tissues. Ectopic TNFRSF9 expression in PDA cells suppressed cell proliferation and migration and induced apoptosis, while TNFRSF9 knockout showed opposing effects. PAX6 was identified as a downstream target of TNFRSF9. TNFRSF9 overexpression in nude mice led to reduced tumor growth. Conclusion: The study suggests that TNFRSF9 may hold promise as a therapeutic target in PDA management, given its potential to inhibit tumor growth and modulate cell behavior.