XIAP Mediated-PTEN Neddylation Promotes Proliferation And Migration Of Colon Cancer Cells

Objective:To explore the functional role of XIAP-PTEN Neddylation axis in colorectal cancer at cell line and clinical level.Methods:The expression level of XIAP was analyzed in tissue microarray of colorectal cancer by immunohistochemical staining,and the protein level of XIAP was detected in human colorectal cancer and adjacent normal tissues by Western blot.Co-IP was performed to analyze the interaction between endogenous PTEN and XIAP in SW480 cell line.CRISPR Cas9 technology was used to construct XIAP-knockout SW480 cell line,and the Neddylation level of PTEN was analyzed in sg-XIAP cells by immunoprecipitation and western blotting.XIAP knockout or wild type SW480 cell lines were co-transfected with FLAG-Vector or FLAG-PTEN-Nedd8 plasmid,then CCK8 and Transwell experiments were used to assay the proliferation and migration of XIAP-PTEN Neddylation axis in SW480 cells,respectively.Results:(1)The expression levels of XIAP are upregulated in colon and rectum cancer tissues compared with adjacent normal tissues.(2)XIAP interacts with PTEN in SW480 colon cancer cells.(3)Deletion of XIAP inhibits PTEN Neddylation in SW480 cells.(4)The level of PTEN Neddylation was elevated in colorectal cancer tissues compared with adjacent normal tissues.(5)Deletion of XIAP inhibits the proliferation and migration of SW480 cells significantly,while PTEN-Nedd8 fusion protein rescue the phenotypes of XIAP deletion in SW480 cells.Conclusion:XIAP-PTEN Neddylation axis promotes SW480 colon cancer cell proliferation and migration.