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微小RNA-101调节EZH2的表达,并促进上皮性卵巢癌的进展和顺铂耐药。

miR-101 regulates expression of EZH2 and contributes to progression of and cisplatin resistance in epithelial ovarian cancer.

作者信息

Liu Lin, Guo Jianfeng, Yu Lili, Cai Jing, Gui Ting, Tang Huijuan, Song Limian, Wang Jia, Han Fang, Yang Chun, Chen Chunyan, Marks Ariel, Wang Zehua

机构信息

Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Tumour Biol. 2014 Dec;35(12):12619-26. doi: 10.1007/s13277-014-2585-6. Epub 2014 Sep 27.

Abstract

In order to determine the expression pattern of miR-101 in epithelial ovarian neoplasms and assess the functions and mechanism of miR-101 in tumorigenesis, we detected the expression of miR-101 and zeste homolog 2 (EZH2) in normal, benign, and malignant ovarian tissues and used miR-101 lentivirus infection to increase miR-101 expression in ovarian cancer cells and drug-resistant cancer cells. We found that miR-101 was underexpressed in epithelial ovarian cancer tissues, which significantly correlated with poor cell differentiation, advanced International Federation of Gynecology and Obstetrics (FIGO) stages, and ovarian cancer cell cisplatin resistance. miR-101 overexpression decreased the expression of EZH2, reduced proliferation and migration of ovarian cancer cells, and resensitized drug-resistant cancer cells to cisplatin-induced cytotoxicity, suggesting the important role miR-101 plays in ovarian cancer that may be associated with its function as a regulator targeting EZH2. Our findings show the potential of miR-101 as a diagnostic marker and new therapeutic target for patients with epithelial ovarian cancer.

摘要

为了确定miR-101在上皮性卵巢肿瘤中的表达模式,并评估miR-101在肿瘤发生中的功能及机制,我们检测了正常、良性及恶性卵巢组织中miR-101和zeste同源物2(EZH2)的表达,并利用miR-101慢病毒感染来提高卵巢癌细胞和耐药癌细胞中miR-101的表达。我们发现,miR-101在上皮性卵巢癌组织中表达下调,这与细胞分化差、国际妇产科联盟(FIGO)分期晚以及卵巢癌细胞顺铂耐药显著相关。miR-101过表达降低了EZH2的表达,减少了卵巢癌细胞的增殖和迁移,并使耐药癌细胞对顺铂诱导的细胞毒性重新敏感,这表明miR-101在卵巢癌中发挥的重要作用可能与其作为靶向EZH2的调节因子的功能有关。我们的研究结果表明,miR-101作为上皮性卵巢癌患者的诊断标志物和新的治疗靶点具有潜力。

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