Methylation-associated Has-miR-9 deregulation in paclitaxel- resistant epithelial ovarian carcinoma

BMC Cancer

Research Article

Yuyan Mao¹  Weiguo Lu¹  Xing Xie¹  Xiaoyun Wan¹  Xiaodong Cheng¹  Xiao Li²  Qianqian Pan³ 

[1] Department of Gynecologic Oncology, Women’s Hospital, School of Medicine, Zhejiang University, No.1 Xueshi Road, 310006, Hangzhou, Zhejiang, China;Women’s Reproductive Health Laboratory of Zhejiang Province, Women’s Hospital, School of Medicine, Zhejiang University, No.1 Xueshi Road, 310006, Hangzhou, Zhejiang, China;Department of Gynecologic Oncology, Women’s Hospital, School of Medicine, Zhejiang University, No.1 Xueshi Road, 310006, Hangzhou, Zhejiang, China;Women’s Reproductive Health Laboratory of Zhejiang Province, Women’s Hospital, School of Medicine, Zhejiang University, No.1 Xueshi Road, 310006, Hangzhou, Zhejiang, China;Zhejiang Financial College, No. 118 Xueyuan Street, 310018, Hangzhou, Zhejiang, China;

关键词: Ovarian carcinoma;    Chemoresistance;    miR-9;    Methylation;   

DOI  :  10.1186/s12885-015-1509-1

 received in 2014-07-14, accepted in 2015-06-19,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundDrug resistance is still one of the key causes of death in epithelial ovarian carcinoma (EOC) patients, however there are very few strategies to reverse chemoresistance. Here we try to clarify whether and how miR-9 takes part in the regulation of paclitaxel sensitivity.MethodsmiR-9 expressions in EOC cells and tissues were detected by Realtime PCR. The target of miR-9 was validated through dual luciferase reporter assay and Western Blot. Methylation study, RNAi technique and cytotoxicity assay were used to determine the intrinsic mechanism of miR-9 in paclitaxel sensitivity regulation.ResultsmiR-9 is down-regulated in paclitaxel resistant EOC. The patients with lower miR-9, Grade 3, Stage III –IV and suboptimal surgery present shorter survival time. miR-9 and suboptimal surgery are independent prognostic factors of EOC. Modulating miR-9 expression could change paclitaxel sensitivity of EOC cells. CCNG1, validated as a direct target of miR-9, mediates paclitaxel resistance. miR-9-1 and 3 gene hypermethylation would decrease miR-9 expression, while demethylation of miR-9 gene could restore miR-9 expression and improve paclitaxel sensitivity in chemoresistance EOC cells. Furthermore, methylation-associated miR-9 deregulation in EOC cells could be induced by paclitaxel exposure.ConclusionsMethylation-associated miR-9 down-regulation is probably one of the key mechanisms for paclitaxel resistance in EOC cells, via targeting CCNG1. Our findings may also provide a new potential therapeutic target to reverse paclitaxel resistance in EOC patients.

【 授权许可】

Unknown   
© li et al. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.