UBE3C在雌激素促进子宫内膜癌细胞迁移及侵袭中的作用机制研究  

UBE3C mediates estrogen-induced migration and invasion in endometrioid carcinoma cells

作　　者：徐华丽 杨孝明 杜娜 杨烨[1] 孙云燕[1] 席晓薇[1] Xu Huali1 ,Yang Xiaoming1,2 ,Du Na1,et al(1. Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080 ;2. Department of Obstetrics and Gynecology, Shanghai Jiaotong University School of Medicine Affiliated International Peace Maternity and Child Health Hospital, Shanghai 20003)

机构地区：[1]上海交通大学附属第一人民医院妇产科,上海200080 [2]上海交通大学医学院附属国际和平妇幼保健院妇产科,上海200030

出　　处：《现代妇产科进展》2018年第5期334-338,342,共6页Progress in Obstetrics and Gynecology

基　　金：国家自然科学基金资助项目(No:81172478);上海市科委生药领域资助项目(No:124119a5400)

摘　　要：目的:探讨泛素连接酶E3C(UBE3C)在雌激素(E_2)诱导子宫内膜癌细胞发生迁移、侵袭及上皮间质转化(EMT)过程中的作用。方法:免疫组化法检测子宫内膜癌组织中UBE3C表达情况。qRT-PCR及Western blot法检测UBE3C在子宫内膜癌细胞株、子宫内膜间质细胞株及正常子宫内膜上皮细胞中的表达。雌激素以浓度及时间梯度处理Ishikawa细胞,qRT-PCR及Western blot法检测UBE3C mRNA和蛋白表达。雌激素处理siNC或siUBE3C转染的Ishikawa细胞,划痕试验和Transwell侵袭实验检测细胞迁移、侵袭能力,Western blot法检测EMT相关蛋白E-cadherin、N-cadherin、snail及slug表达。结果:UBE3C在子宫内膜癌组织及细胞中高表达。雌激素能上调Ishikawa细胞UBE3C mRNA及蛋白表达,且在一定范围内呈剂量时间依赖性。雌激素刺激增强Ishikawa细胞的迁移、侵袭能力,促进EMT;si-UBE3C干扰能显著抑制上述作用,且能减弱雌激素对Ishikawa细胞迁移、侵袭能力的增强及EMT的促进。结论:UBE3C与雌激素能增强子宫内膜癌细胞的迁移、侵袭能力,促进上皮间质转化,UBE3C可能是雌激素下游重要的靶基因之一,介导雌激素诱导子宫内膜癌细胞的迁移、侵袭及上皮间质转化。Objective： To explore the role of ubiquitin ligase E3C（ UBE3C） on estrogen-induced migration,invasion and epithelial-mesenchymal transition（ EMT） in endometrial carcinoma cells.Methods： Immunohistochemistry was used to analyze the expression of UBE3C in endometrioid carcinoma tissues. The expression of UBE3C was investigated in endometrial carcinoma cell lines,endometrial stromal cell line and primary-cultured normal endometrial epithelium cells by qRT-PCR and Western blot.Endometrial carcinoma cell line Ishikawa was treated with estrogen in dose-and time-dependent manner,qRT-PCR and Western blot were used to analyze the expression levels of mRNA and protein of UBE3 C.Ishikawa was stimulated with estrogen or not when transfected with si-NC or si-UBE3C.Wound healing assay and cell invasion assay were used to investigate the migration and invasion abilities of cells.Western blot was used to find out the changes of protein levels of EMT-related molecules E-cadherin,N-cadherin,snail and slug.Results： Overexpression of UBE3C was observed in endometrial carcinoma tissues and cell lines.Estrogen upregulated the expression of UBE3C in a dose-and time-dependent manner in Ishikawa cells.Estrogen stimulation enhanced the abilities of migration,invasion and promoted EMT in Ishikawa,while decreased UBE3C by si-UBE3C interfering inhibited the process of EMT and weakened the migration and invasion abilities.Furthermore,ablation of UBE3C significantly reversed estrogen-induced migration,invasion and EMT in Ishikawa.Conclusion：UBE3C and estrogen both promote the process of migration,invasion and EMT in endometrial carcinoma cells.UBE3C mediated estrogen-induced migration,invasion and EMT,and may play a critical role in endometrial carcinoma as a target of estrogen.

关 键 词：泛素连接酶E3C 雌激素 子宫内膜癌 迁移 侵袭 上皮间质转化 

分 类 号：R737.33[医药卫生—肿瘤]