title: MicroRNA-186 induces sensitivity of ovarian cancer cells to paclitaxel and cisplatin by targeting ABCB1.
abstract: BACKGROUND
  Recent studies have shown that microRNAs may regulate the ABCB1 gene (ATP-binding cassette, sub-family B [MDR/TAP], member 1). Computational programs have predicted that the 3'-untranslated region (3'-UTR) of ABCB1 contains a potential miRNA-binding site for miR-186. Here, we investigated the role of miR-186 in sensitizing ovarian cancer cells to paclitaxel and cisplatin.
  
  
  RESULTS
  Human ovarian carcinoma cell lines OVCAR3, A2780, A2780/DDP, and A2780/Taxol were exposed to paclitaxel or cisplatin with or without miR-186 transfection, and cell viability was determined by MTT assay. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis were used to assess the MDR1, GST-π, and MRP1 expression levels. Dual-luciferase reporter assay was used to reveal the correlation between miR-186 and ABCB1. Lower miR-186 while higher MDR1 and GST-π mRNA expression levels were found in the A2780/Taxol and A2780/DDP cells than in the A2780 cells. After miR-186 transfection, all the cell lines showed increased sensitivity to paclitaxel and cisplatin. MiR-186 transfection induced apoptosis while anti-miR-186 transfection reduced apoptosis. The dual-luciferase reporter assay verified that that miR-186 combined with the 3'-untranslated region (UTR) of ABCB1. MDR1 and GST-π mRNA and protein expression levels were downregulated after transfection with miR-186 but upregulated following anti-miR-186 transfection compared to the mock and negative control cancer cells; however, the MRP1 expression levels did not significantly differ among the groups.
  
  
  CONCLUSIONS
  Our results are the first to demonstrate that miR-186 may sensitize ovarian cancer cell to paclitaxel and cisplatin by targeting ABCB1 and modulating the expression of GST-π.
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, P.R. China. sunkx90@163.com.
authors.forename: Kai-Xuan
authors.initials: KX
authors.lastname: Sun
authors.affiliation: Department of Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, P.R. China. jiaojinwen@126.com.
authors.forename: Jin-Wen
authors.initials: JW
authors.lastname: Jiao
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, P.R. China. chenshuo077003@163.com.
authors.forename: Shuo
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, P.R. China. fkliuboliang@sina.com.
authors.forename: Bo-Liang
authors.initials: BL
authors.lastname: Liu
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, P.R. China. yida.zhaoyang@163.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use*; D015536:Down-Regulation / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000037:antagonists & inhibitors; D035683:MicroRNAs / Q000378:metabolism / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000627:therapeutic use*; D014162:Transfection
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; C533096:MIRN186 microRNA, human; D035683:MicroRNAs; D008156:Luciferases; D005982:Glutathione Transferase; D017239:Paclitaxel; D002945:Cisplatin