Micro-RNAs associated with the evolution of ovarian cancer cisplatin resistance

•Cisplatin resistance in OVCA cell lines is associated with 9 miRNAs.•Phenotypically EMT cells are associated with more chemo-resistant cancers.•TGF/WNT and Development Regulation of EMT are associated with overall survival.

ObjectivesOvarian 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.MethodsIn this study, four OVCA cell lines (A2780CP, A2780S, IGROV1, and OVCAR5) were serially treated with cisplatin in parallel with measurements of miRNA expression changes.ResultsNine 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.ConclusionsCollectively, 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.