title: Deregulation of miR-128 in ovarian cancer promotes cisplatin resistance.
abstract: OBJECTIVE
  Platinum-based chemotherapy is the standard treatment in advanced ovarian cancer, but most patients will relapse with drug-resistant disease. MicroRNAs have been demonstrated to function in chemoresistance in cancers. In this study, we focused on the role of miR-128 in cisplatin-resistant ovarian cancer.
  
  
  METHODS
  The expression of miR-128 RNA and its targeted genes, the polycomb ring finger oncogene Bmi-1 and ATP-binding cassette subfamily C member 5 (ABCC5), were investigated in the epithelial ovarian cancer cells and ovarian carcinomas.
  
  
  RESULTS
  miR-128 expression was significantly reduced in the cisplatin-resistant human epithelial ovarian cancer cell line SKOV3/CP compared with parental SKOV3 cells and decreased upon treatment with cisplatin in a concentration-dependent manner in SKOV3, OVCAR3, and PEO14 cells. Overexpression of miR-128 resensitized SKOV3/CP cells to cisplatin and reduced the expression of cisplatin-resistant-related proteins ABCC5 and Bmi-1, whereas miR-128 inhibitors increased cisplatin resistance in SKOV3 cells. Cisplatin combined with miR-128 agomirs inhibited the growth of SKOV3/CP xenograft tumors more effectively than cisplatin alone. Diminished expression of ABCC5 and Bmi-1 and higher cisplatin concentrations were observed in tumor tissue of mice treated with miR-128 agomirs in addition to cisplatin.
  
  
  CONCLUSIONS
  Taken together, our findings suggest that miR-128 may act as a promising therapeutic target for improvement of tumor sensitivity to cisplatin.
authors.affiliation: Departments of *Gynecology and Obstetrics, and †Anesthesiology, the Military General Hospital of Beijing PLA, Beijng, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.forename: Nan
authors.initials: N
authors.lastname: Wu
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Zhang
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Shang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; C545189:MIRN128 microRNA, human; D035683:MicroRNAs; D002945:Cisplatin