Bernadette M Boac1, Yin Xiong2, Douglas C Marchion3, Forough Abbasi2, Stephen H Bush1, Ingrid J Ramirez1, Beman R Khulpateea1, E Clair McClung1, Amy L Berry1, Nadim Bou Zgheib1, Hye Sook Chon4, Mian M Shahzad4, Patricia L Judson5, Robert M Wenham5, Sachin M Apte4, Anders E Berglund6, Anthony M Magliocco7, Johnathan M Lancaster8. 1. Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA. 2. 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. 3. 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. 4. 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. 5. 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. 6. Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA. 7. 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. 8. Myriad Genetic Laboratories, Salt Lake City, UT 84108, USA.
Abstract
OBJECTIVES: 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.
OBJECTIVES: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: Weixin Wang; Meghan Corrigan-Cummins; Justin Hudson; Irina Maric; Olga Simakova; Sattva S Neelapu; Larry W Kwak; John E Janik; Barry Gause; Elaine S Jaffe; Katherine R Calvo Journal: Haematologica Date: 2011-11-18 Impact factor: 9.941
Authors: Angela B Y Hui; Alice Lin; Wei Xu; Levi Waldron; Bayardo Perez-Ordonez; Ilan Weinreb; Wei Shi; Jeff Bruce; Shao Hui Huang; Brian O'Sullivan; John Waldron; Patrick Gullane; Jonathan C Irish; Kelvin Chan; Fei-Fei Liu Journal: Clin Cancer Res Date: 2013-03-04 Impact factor: 12.531
Authors: Cheng-Han Lee; Subbaya Subramanian; Andrew H Beck; Inigo Espinosa; Janine Senz; Shirley X Zhu; David Huntsman; Matt van de Rijn; C Blake Gilks Journal: PLoS One Date: 2009-10-02 Impact factor: 3.240