中国肿瘤生物治疗杂志2025，Vol.32Issue(12)：1253-1261,9.DOI:10.3872/j.issn.1007-385x.2025.12.006
USP20通过稳定TWIST促进胰腺癌细胞增殖与迁移
USP20 promotes pancreatic cancer cell proliferation and migration by stabilizing TWIST
摘要
Abstract
Objective:To investigate the expression of ubiquitin-specific protease 20(USP20)in pancreatic cancer tissues and its role and molecular mechanism in the proliferation and migration of pancreatic cancer cells.Methods:The Cancer Genome Atlas(TCGA)database was used to analyze USP20 and TWIST family bHLH transcription factor(TWIST)expression in pancreatic cancer tissues.Kaplan-Meier curve analysis was used evaluate their correlation with patient prognosis.Normal pancreatic cells(HPNE)and pancreatic cancer cells(MIAPaca2,BxPC3,PANC1,SW1990,Aspc1)were routinely cultured,and USP20 protein expression was detected by Western blot(WB).PANC1 and SW1990 cells were divided into shNC,shUSP20-1,and shUSP20-2 groups,and transfected with corresponding lentiviruses.Knockdown efficiency was verified by qPCR and WB.Cell proliferation,migration,and cell cycle distribution were assessed using CCK-8,colony formation,wound healing,Transwell assays,and flow cytometry,respectively.WB was used to detect the expression of epithelial-mesenchymal transition(EMT)-related transcription factors.Co-immunoprecipitation(Co-IP)and ubiquitination assays were conducted to determine whether USP20 interacts with TWIST and regulates its expression via the ubiquitination pathway.Results:USP20 and TWIST mRNA levels were significantly upregulated in pancreatic cancer tissues(both P<0.05),and their levels were negatively correlated with patient prognosis(both P<0.05).USP20 protein was highly expressed in PANC1,SW1990,MIAPaca2,and BxPC3 cells(all P<0.001).Knockdown of USP20 significantly inhibited the proliferation and migration of PANC1 and SW1990 cells(all P<0.001).USP20 interacted with TWIST(P<0.05 or P<0.01)and stabilized TWIST expression by reducing its ubiquitination level(P<0.01).Conclusion:USP20 is highly expressed in pancreatic cancer tissues and promotes pancreatic cancer cell proliferation and migration by stabilizing TWIST through deubiquitination.These findings suggest that USP20 may serve as a potential diagnostic and therapeutic target in the treatment of pancreatic cancer.关键词
泛素特异性蛋白酶20/扭曲家族碱性螺旋-环-螺旋转录因子/胰腺癌/增殖/迁移/去泛素化Key words
ubiquitin-specific protease 20(USP20)/Twist family BHLH transcription factor(TWIST)/pancreatic cancer/proliferation/migration/deubiquitination分类
医药卫生引用本文复制引用
汤佩佩,刘凌,李春梅,季润元,傅玉峰,陈松..USP20通过稳定TWIST促进胰腺癌细胞增殖与迁移[J].中国肿瘤生物治疗杂志,2025,32(12):1253-1261,9.基金项目
国家自然科学基金(No.U2004138) （No.U2004138）
江苏省高等学校自然科学研究项目(No.21KJD310002) （No.21KJD310002）
江苏省青蓝工程优秀教学团队(No.2022-25) （No.2022-25）
