Integrative microRNA and gene expression analysis identifies new epigenetically regulated microRNAs mediating taxane resistance in ovarian cancer

Abstract Taxane is a family of front-line chemotherapeutic agents against ovarian cancer (OC). The therapeutic efficacy frequently counteracted by the development chemoresistance, leading to high rates relapse in OC patients. role(s) microRNAs (miRNAs) chemoresistance had been supported many evidences Epigenetic regulation miRNAs has reported influence and response therapeutics, however, their role resistance paclitaxel (PTX) unclear. Here, we conducted miRNA profiling responsive PTX-resistant cell lines before after treatment with epigenetic modulators. We reveal 157 be downregulated cells compared parental controls. expression five (miRNA-7-5p, -204-3p, -501-5p, -3652 -4286) was restored modulation, which further confirmed qPCR. In silico analysis signaling pathways targeted selected identified PI3K-AKT pathway as primary target. Subsequent cDNA array multiple members such AKT2, PIK3R3, CDKN1A, CCND2 FGF2 upregulated cells. STRING showed deregulated genes primarily involved cycle progression survival. Thus, throughput coupled data mining provide evidence for epigenetically regulated miRNAs-induced modulation PTX resistant It paves way more in-depth mechanistic studies new strategies combat chemoresistance.