title: Micro-RNAs associated with the evolution of ovarian cancer cisplatin resistance.
abstract: OBJECTIVE
  Ovarian cancer (OVCA) is the leading cause of mortality among women with gynecologic malignancy, in part due to the development of chemoresistance. We sought to identify micro-RNAs (miRNAs) associated with in vitro development of OVCA chemoresistance that may also represent potential targets for therapy.
  
  
  METHODS
  In this study, four OVCA cell lines (A2780CP, A2780S, IGROV1, and OVCAR5) were serially treated with cisplatin in parallel with measurements of miRNA expression changes.
  
  
  RESULTS
  Nine miRNAs were found to be associated with increasing cisplatin resistance (IC50) (p<0.01); however, only 5 of these miRNAs have publically available information. Pathway analysis identified 15 molecular signaling pathways that were represented by genes predicted to be targets of the 5 miRNAs (false discovery rate<0.05), 11 of which are associated with the epithelial-mesenchymal transition (EMT). Further analysis identified 2 of those pathways as being associated with overall survival in 218 patients with OVCA.
  
  
  CONCLUSIONS
  Collectively, this panel of miRNAs associated with in vitro evolution of OVCA cisplatin resistance and the pathways identified to be associated with EMT and overall patient survival provide a framework for further investigations into EMT as a therapeutic target in patients with OVCA.
authors.affiliation: Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors.forename: Bernadette M
authors.initials: BM
authors.lastname: Boac
authors.affiliation: Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors.forename: Yin
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA. Electronic address: douglas.marchion@moffitt.org.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Marchion
authors.affiliation: Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors.forename: Forough
authors.initials: F
authors.lastname: Abbasi
authors.affiliation: Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Bush
authors.affiliation: Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors.forename: Ingrid J
authors.initials: IJ
authors.lastname: Ramirez
authors.affiliation: Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors.forename: Beman R
authors.initials: BR
authors.lastname: Khulpateea
authors.affiliation: Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors.forename: E
authors.initials: E
authors.lastname: Clair McClung
authors.affiliation: Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Berry
authors.affiliation: Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors.forename: Nadim
authors.initials: N
authors.lastname: Bou Zgheib
authors.affiliation: Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Department of Oncologic Sciences, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Chon
authors.affiliation: Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Department of Oncologic Sciences, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors.forename: Mian M
authors.initials: MM
authors.lastname: Shahzad
authors.affiliation: Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Department of Oncologic Sciences, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Judson
authors.affiliation: Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Department of Oncologic Sciences, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Wenham
authors.affiliation: Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Department of Oncologic Sciences, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors.forename: Sachin M
authors.initials: SM
authors.lastname: Apte
authors.affiliation: Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors.forename: Anders E
authors.initials: AE
authors.lastname: Berglund
authors.affiliation: Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Department of Oncologic Sciences, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Department of Anatomic Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Magliocco
authors.affiliation: Myriad Genetic Laboratories, Salt Lake City, UT 84108, USA.
authors.forename: Johnathan M
authors.initials: JM
authors.lastname: Lancaster
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D035683:MicroRNAs; D002945:Cisplatin
keywords: Chemoresistance; Epithelial–mesenchymal transition; Micro-RNA; Ovarian cancer