title: Methylation-associated Has-miR-9 deregulation in paclitaxel- resistant epithelial ovarian carcinoma.
abstract: BACKGROUND
  Drug 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.
  
  
  METHODS
  miR-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.
  
  
  RESULTS
  miR-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.
  
  
  CONCLUSIONS
  Methylation-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.
authors.affiliation: Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, No.1 Xueshi Road, 310006, Hangzhou, Zhejiang, China. lixsure@163.com.|Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, No.1 Xueshi Road, 310006, Hangzhou, Zhejiang, China. lixsure@163.com.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, No.1 Xueshi Road, 310006, Hangzhou, Zhejiang, China. panqianqian831107@sina.com.|Zhejiang Financial College, No. 118 Xueyuan Street, 310018, Hangzhou, Zhejiang, China. panqianqian831107@sina.com.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, No.1 Xueshi Road, 310006, Hangzhou, Zhejiang, China. wanxy@zju.edu.cn.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Wan
authors.affiliation: Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, No.1 Xueshi Road, 310006, Hangzhou, Zhejiang, China. maoyy3@alyun.com.
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, No.1 Xueshi Road, 310006, Hangzhou, Zhejiang, China. lbwg@zju.edu.cn.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, No.1 Xueshi Road, 310006, Hangzhou, Zhejiang, China. xiex@zju.edu.cn.
authors.forename: Xing
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, No.1 Xueshi Road, 310006, Hangzhou, Zhejiang, China. chengxd@zju.edu.cn.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Cheng
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D056766:Cyclin G1 / Q000235:genetics; D019175:DNA Methylation; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056426:Genetic Loci; D006801:Humans; D008745:Methylation; D035683:MicroRNAs / Q000235:genetics*; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*; D011379:Prognosis; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C534702:CCNG1 protein, human; D056766:Cyclin G1; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D017239:Paclitaxel