Deubiquitinating enzyme USP14 promotes endometrial cancer cell proliferation and epithelial mesenchymal transformation via stabilizing β-catenin protein
Deubiquitinating enzyme USP14 promotes endometrial cancer cell proliferation and epithelial mesenchymal transformation via stabilizing β-catenin protein
This study was designed to investigate the biological function and interaction mechanism of deubiquitinating enzyme USP14 and β-catenin in endometrial carcinoma(EC).The expression of USP14 and β-catenin in EC tissues and adjacent healthy tissues were detected by real-time fluorescence quantitative PCR and immunohistochemistry,while the effects of USP14 on β-catenin protein stability and ubiquitination were investigated by Western blotting and protein immunoprecipitation using HEA-1C and Ishikawa cell lines derived from EC.The effect of USP14 and β-catenin on EC cell proliferation was verified by cell proliferation assay(CCK-8);the regulatory effect of USP14 on β-catenin was verified by plasmid transfection.The regulation of USP14 and β-catenin on the expression of proteins related to epithelial-mesenchymal transition(EMT)in EC cells were verified by Western blotting.Data showed that the expression of USP14 and β-catenin in EC tissues were higher than those in adjacent healthy tissues,and USP14 and β-catenin interacted in EC cell line.USP14 maintained the protein stability of β-catenin through its deubiquitination activity.USP14-specific inhibitors could enhance the ubiquitination level of β-catenin and down-regulate the expression of β-catenin.USP14-specific inhibitors also inhibited EC cell proliferation and inhibited the expression of EMT-related proteins,while overexpression of β-catenin reversed the inhibition of EC cell growth and EMT induced by USP14 inhibitors.In conclusion,USP14 maintains β-catenin protein stability in EC cells by regulating the ubiquitination level,and the regulation of cell proliferation and EMT requires β-catenin.
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