The Biological Function Of ZIP4 And Its Mechanism In Gallbladder Cancer

Background and purpose: Gallbladder Cancer(GBC)is a common gastrointestinal cancer with high aggressive and extremely poor prognosis.ZIP4 is one of the Zn transporter families SLC39A/ZIP.The abnormal expression of ZIP4 was found in human cancers,including pancreatic cancer and liver cancer.But,the significance of ZIP4 in gallbladder cancer is still unclear.In this study,our purpose is to study the biological function and molecular mechanism of ZIP4 in gallbladder cancer and support a new genetic treatment target in GBC patients.Methods: Firstly,we determined the expression in 41 GBC and adjacent tissues by real-time quantitative PCR and analyzed the relationship between ZIP4 expression and histology and clinical factors by Fisher's exact test and " tests.The Cox proportional hazards model was used to measure the survival in GBC patients.Secondly,Cell proliferation ability and invasiveness were evaluated by using CCK8 assay,colony formation,transwell invasion and migration assay in vitro.Lastly,subcutaneous xenograft tumor models in nude mice by using ZIP4-knockdown and wild type NOZ cells.Results: The expression of ZIP4 was significantly increased in GBC tissues.Multivariate analyses confirmed that ZIP4 overexpression was negatively correlated with overall survival.Besides,down-regulation of ZIP4 expression resulted in the obvious inhibition of proliferation,invasion and migration both in vitro and in vivo which caused cell cycle arrest in G0/G1 with the declined expression of Cyclin D1.Conclusion: ZIP4 enhanced cell proliferation,migration and invasion and could serve as a genetic treatment target in GBC patients in future.