UBE2T对乳腺癌细胞增殖、凋亡及上皮-间质转化的影响  

Effects of UBE2T on Proliferation,Apoptosis,and Epithelial-Mesenchymal Transition of Breast Cancer Cells

作　　者：刘思琪 孙欣[1] 刘娜[1] 林方才[1] LIU Siqi;SUN Xin;LIU Na;LIN Fangcai(Department of Breast Surgery,Capital Medical University Electric Power Teaching Hospital,Beijing 100071,China)

机构地区：[1]首都医科大学北京电力教学医院乳腺科,北京100071

出　　处：《肿瘤防治研究》2025年第4期281-289,共9页Cancer Research on Prevention and Treatment

基　　金：国中康健集团科技项目(Y2022011)。

摘　　要：目的探究泛素结合酶E2T(UBE2T)在乳腺癌中的表达和对预后的影响及其可能的作用机制。方法采用肿瘤基因组图谱(TCGA)数据库分析UBE2T在乳腺癌组织中的表达情况,Kaplan-Meier生存曲线分析UBE2T高低表达对无病生存期(DFS)和总生存期(OS)的影响。实时定量PCR和Western blot验证UBE2T敲降和过表达效率,分析其对肿瘤细胞生物学行为的影响,Western blot研究UBE2T对细胞上皮-间质转化(EMT)的作用。构建异种移植瘤模型,验证敲降UBE2T对乳腺癌细胞在体内生长的影响。结果UBE2T在乳腺癌组织和癌旁组织的表达量差异具有统计学意义(P<0.001),在远处转移或分期较晚的乳腺癌患者中表达量较高(均P<0.05),且UBE2T高表达组的DFS和OS降低(均P<0.05)。UBE2T在MCF-7、MDA-MB-231细胞中高表达,在MDA-MB-361细胞中低表达(均P<0.01)。敲降UBE2T后肿瘤细胞增殖能力显著下降,而上调UBE2T表达后细胞增殖能力增强(均P<0.05);沉默组MCF-7、MDA-MB-231细胞凋亡率均较shNC组显著升高,过表达组MAD-MB-361细胞凋亡率下降(均P<0.001);敲降组细胞迁移率较shNC组降低,而过表达组细胞迁移率显著增加(均P<0.01)。此外,敲降组细胞迁移数和侵袭数均低于shNC组,过表达组细胞迁移数和侵袭数均高于对照组(均P<0.01)。下调UBE2T可以降低N-cadherin、Snail和Vim-entin的表达(均P<0.05),升高E-cadherin的表达,而上调UBE2T表达则相反(均P<0.01);但TIMER数据库分析结果提示,UBE2T表达与E-cadherin(P<0.001)、N-cadhe-rin(P=0.013)、Snail(P<0.001)正相关,与Vimentin负相关(P<0.001)。体内实验表明下调UBE2T可以减缓移植瘤的生长速度。结论UBE2T在乳腺癌组织中高表达并影响患者预后,UBE2T可以促进乳腺癌细胞的增殖,并抑制凋亡,同时通过改变EMT相关蛋白的表达,增强肿瘤细胞迁移和侵袭的能力。Objective To investigate the expression of ubiquitin binding enzyme E2T(UBE2T)in breast cancer(BRCA)and its role and mechanism in the prognosis of BRCA patients.Methods The Tumor Genome Atlas(TCGA)database was used to analyze UBE2T expression in BRCA tissues,and the effects of UBE2T expression on disease-free survival(DFS)and overall survival(OS)were analyzed by Kaplan-Meier(KM)survival curve.In vitro,real-time quantitative PCR and Western blot were used to confirm the knockdown and overexpression efficiency,to analyze its effect on tumor cell biological behavior.The effect of UBE2T on cell epithelial–mesenchymal transition(EMT)was studied by Western blot.A xenograft tumor model was established to verify the effect of UBE2T knockdown on the growth of BRCA cells in vivo.Results The UBE2T expression levels in BRCA and adjacent tissues were statistically different(P<0.001),and the expression was increased in tissues with distant metastasis or late stage(all P<0.05).The DFS and OS were decreased in the UBE2T high-level group(both P<0.05).UBE2T was highly expressed in MCF-7 and MDA-MB-231 cells and lowly expressed in MDA-MB-361 cells(all P<0.01).After UBE2T was silenced by shRNA,the proliferation ability of tumor cells significantly decreased,whereas it increased after UBE2T upexpression(all P<0.05).The apoptotic rates of MCF-7 and MDA-MB-231 cells in the silent groups were significantly higher than those in the shNC groups,while the apoptotic rates of MAD-MB-361 cells in the overexpression group decreased(all P<0.001).The mobility in the knockdown groups were lower than in the shNC groups,while the mobility in the overexpression group significantly increased(both P<0.01).The migration and invasion cells in the shUBE2T groups were lower than those in the shNC groups,and the migration and invasion cells in the UBE2T group were higher than those in the vector group(all P<0.01).Downregulation of UBE2T decreased the expression levels of N-cadherin,Snail,and Vimentin(all P<0.05)and increased that of E-cadherin;however,th

关 键 词：乳腺癌 UBE2T 预后 增殖 迁移 侵袭 EMT 

分 类 号：R73-37[医药卫生—肿瘤] R737.9[医药卫生—临床医学]