CUL4A促进人卵巢癌细胞侵袭转移及其机制探讨  

Effect and mechanism of CUL4A on migration and invasion in ovarian cancer cells

作　　者：韩小妮 方念[2] 孙玉芳[1] 戴星[1] 胡鸣[1] 焦榕芳[1] 周静[1] 

机构地区：[1]南昌大学第四附属医院妇产科,南昌330003 [2]南昌大学第四附属医院消化内科,南昌330003

出　　处：《现代妇产科进展》2015年第12期889-892,897,共5页Progress in Obstetrics and Gynecology

基　　金：江西省卫生厅科技计划(No:20131101);江西省科技支撑计划(No:20142BBG70076)

摘　　要：目的:检测Cullin 4A(CUL4A)表达对卵巢癌细胞迁移及侵袭能力的影响,并初步探讨其相关分子机制。方法:Western blot法检测人卵巢癌细胞株中CUL4A表达,设计合成靶向CUL4A的特异性shRNA,构建稳定低表达CUL4A的卵巢癌细胞株。Western blot和荧光定量PCR验证干扰效率;划痕实验及Transwell法检测下调CUL4A后细胞的迁移及侵袭能力;Western blot和荧光定量PCR检测上皮间质转化(EMT)相关指标及上游信号分子Snail、ZEB1变化。结果:SKOV-3、OV2008、ES-2、OVCAR-3卵巢癌细胞中CUL4A表达均高于正常卵巢上皮细胞HOSE,且以SKOV-3表达水平最高。shRNA转染SKOV-3细胞后,CUL4A的mRNA及蛋白水平显著下降,细胞迁移和侵袭能力明显受到抑制;E-cadherin表达增加,N-cadherin、Vimentin、Snail和ZEB1表达均显著降低。结论:CUL4A可促进卵巢癌细胞的迁移和侵袭,其分子机制可能与调节EMT的上游信号分子Snail及ZEB1有关,提示CUL4A在卵巢癌的发生发展中起着重要的作用。Objective：To detect the effects of CUIAA on migration and invasion of o- varian cancer cells and explore the molecular mechanism. Methods：The expression of CUIAA in ovarian cancer cell and normal ovarian epithelial cell were analyzed by Western blot. shRNA targeting CUIAA was designed and synthesized, and then transfected into SKOV-3 ceils. West- ern blot and Real-time PCR were used to detect the expression of CUIAA after transfection. The Wound Healing assay and Transwell assay were performed to analyze the ability of migration and invasion. The expression of E-cadherin, N-cadherin, Vimentin, Snail and ZEB1 were detected by Western blot and Real-time PCR. Results： The expressions of CUIAA in four ovarian cancer cell lines were higher than the normal ovarian epithelial cell line. The mRNA and protein levels of CUIAA were significantly decreased after transfected with shRNA targeting CUL4A. The migration and invasion ability were significantly inhibited after transfection. In addition, the expression of E-cadherin increased, while N-cadherin, Vimentin, Snail and ZEB1 decreased after transfection. Conclusion： CUL4A could promotes migration and invasion of ovarian cancer cells via regulating upstream factors of EMT,suggesting that CUIAA plays an important role in the development of ovarian cancer.

关 键 词：CUL4A 卵巢癌 细胞迁移 细胞侵袭 上皮间质转化(EMT) 

分 类 号：R737.31[医药卫生—肿瘤]