ZNF281 Promotes Growth and Invasion of Pancreatic Cancer Cells by Activating Wnt/[beta]-Catenin Signaling

Background Zinc finger protein 281 (ZNF281) has been identified to be involved in embryonic stem cell differentiation and tissue development. Also, ZNF281 was found in various types of cancers. However, its biological functions and clinical significance in pancreatic cancer remain elusive. Aims To explore the role of ZNF281 in pancreatic cancer cells proliferation and invasion. Methods ZNF281 expression was examined in public database Oncomine and cBioPortal. The correlation between ZNF281 and clinicopathological features was measured, and Kaplan-Meier method was used to measure the overall survival and recurrence-free survival in the TCGA cohort. Ectopic expression and knockdown of ZNF281 were performed to measure the impact on cell proliferation and invasion. Western blot and immunoprecipitation were further used to identify the ZNF281 interacting proteins. Topflash luciferase assay was used to detect the Wnt/[beta]-catenin signaling activation. Results ZNF281 was predominantly up-regulated in pancreatic cancer tissues and significantly associated with advanced stage. Meanwhile, the high expression of ZNF281 indicated shorter overall survival and recurrence-free survival and ZNF281 could be an independent prognostic factor of pancreatic cancer. ZNF281 promoted cell proliferation and invasion in vitro. Mechanically, ZNF281 activated Wnt/[beta]-catenin signaling and induced the downstream gene expression by directly binding with [beta]-catenin and decreasing the polyubiquitination. Conclusions ZNF281 promotes pancreatic cancer cells proliferation and invasion by interacting and up-regulating [beta]-catenin, highlighting the role of ZNF281 in pancreatic cancer progression.