miR-200a靶向雌孕激素受体抑制子宫内膜癌细胞生长的作用研究  

miR-200a targets estrogen and progesterone receptors to inhibit the growth of endometrial cancer cells

作　　者：张广平[1] 龚时鹏[2] 邓婉文 陈咏宁 廖亚男 孙丽丽[1] 张雅迪 Zhang Guangping;Gong Shipeng;Deng Wanwen(Department of Gynecology,People's Hospital of Huadu District,Guangzhou 510800;Department of Obstetrics and Gynecology,Nanfang Hospital,Southern Medical University,Guangzhou 510515;Health Center of Jianggao Town,Guangzhou 510450)

机构地区：[1]广州市花都区人民医院妇科,广州510800 [2]南方医科大学南方医院妇产科,广州510515 [3]白云区江高镇卫生院,广州510450

出　　处：《现代妇产科进展》2018年第12期886-890,895,共6页Progress in Obstetrics and Gynecology

基　　金：花都区科技计划产学研协同创新重点专项(No:HD15CXY006)

摘　　要：目的:探讨miR-200a对子宫内膜癌细胞雌孕激素受体的靶向作用及生长的影响。方法:选取两种人子宫内膜癌细胞株KLE和Ishikawa,q PCR法检测miR-200a、ESR1和PGR含量,Western blot法检测ER和PR表达。分别在Ishikawa、KLE细胞株中敲除、过表达miR-200a,检测miR-200a对Ishikawa细胞中ESR1和PGR mRNA含量,以及ER和PR表达水平的影响。采用MTT、流式细胞仪、细胞划痕实验和Transwell实验检测miR-200a对细胞增殖、凋亡、迁移和侵袭的影响。结果:Ishikawa细胞中miR-200a、ESR1和PGR含量及ER和PR表达水平均高于KLE细胞(P<0.01)。敲除miR-200a后,可降低Ishikawa细胞中ESR1和PGR含量及ER和PR表达水平(P<0.01)。敲除miR-200a后,细胞的增殖、迁移和侵袭能力增强,细胞凋亡水平下降,过表达miR-200a则呈相反效应(P<0.01)。给予他莫昔芬和RU-486后,上述效应均被一定程度逆转(P<0.01)。结论:miR-200a可靶向作用于子宫内膜癌细胞雌孕激素受体,进而抑制细胞的增殖、迁移和侵袭,有效促进细胞的凋亡。Objective: To investigate the effect of miR-200 a on the estrogen receptor and progesterone receptor in endometrial cancer cells and its effect on their growth. Methods:Two kids of human endometrial cancer cell lines KLE and Ishikawa were selected and the expressions of miR-200 a,ESR1 and PGR mRNA were detected by q PCR.Western blot was used to detect the expressions of ER and PR protein in Ishikawa cells. The miR-200 a gene was knocked out and upregulated in Ishikawa and KLE cell lines,respectively,and the expression levels of ESR1 and PGR mRNA,as well as ER and PR proteins in Ishikawa cell were detected.MTT assay,flow cytometry,cell scratch assay and Transwell assay were used to detect the effects of miR-200 a on cell proliferation,apoptosis,migration and invasion,respectively. Results: The expressions of miR-200 a,ESR1 and PGR mRNA in Ishikawa cells were significantly higher than those in KLE cells,and the expressions of ER and PR protein were also significantly higher than those of KLE cells( P < 0. 01). Knocking down miR-200 a significantly decreased the expressions of ESR1 and PGR mRNA,and also significantly reduced the expression levels of ER and PR protein in Ishikawa cells( P<0.01).The proliferation,migration and invasion ability of both two cells were enhanced and the level of apoptosis was decreased after the knockout ofmiR-200 a,while overexpression of miR-200 a had the opposite effects( P<0.01).After treatment with tamoxifen and RU-486,the above effects were reversed to some extent( P<0.01).Conclusion: miR-200 a can target the estrogen and progesterone receptors of endometrial cancer cells,thereby inhibiting cell proliferation,migration and invasion,and inducing cell apoptosis.

关 键 词：miR-200a 子宫内膜癌 雌激素受体 孕激素受体 

分 类 号：R737.33[医药卫生—肿瘤]