Identification of exosomal and non‑exosomal microRNAs associated with the drug resistance of ovarian cancer.

MicroRNAs (miRNAs) serve important roles in drug-resistance; however, exosomal miRNAs associated with drug-resistance in ovarian cancer (OC) have not been reported to date. The current study aimed to analyze the drug resistance-associated exosomal miRNAs in original OC cells and their derived exosomes using microarray data downloaded from the Gene Expression Omnibus database (series GSE76449). The chemosensitive OC cell lines SKOV3_ip1, A2780_PAR and HEYA8, as well as the chemoresistant cell lines SKOV3_TR, A2780_CP20 and HEYA8_MDR, were investigated. Differentially expressed miRNAs (DE-miRNAs) were identified using the limma method, and their mRNA targets were predicted using the miRWalk and LinkedOmics database. Functions of target genes were analyzed with DAVID tool, while TCGA data were used to explore the survival association of identified miRNAs. According to the results, 28 DE-miRNAs were found to be common in exosomal and original samples of A2780_CP20 cells, among which the functions of 5 miRNAs were predicted (including miR-146b-5p, miR-509-5p, miR-574-3p, miR-574-5p and miR-760). In addition, 16 and 35 DE-miRNAs were detected for HEYA8_MDR and SKOV3_TR, respectively, with the functions of 4 of these miRNAs predicted for each cell line (HEYA8_MDR: miR-30a-3p, miR-30a-5p, miR-612 and miR-617; SKOV3_TR: miR-193a-5p, miR-423-3p, miR-769-5p and miR-922). It was also reported that miR-183-5p was the only one common miRNA among the three cell lines. Furthermore, miR-574-3p, miR-30a-5p and miR-922 may regulate CUL2 to mediate HIF-1 cancer signaling pathway, while miR-183-5p may modulate MECP2, similar to miR-760, miR-30a-5p and miR-922, to influence cell proliferation. Finally, the downregulated miR-612 may promote the expression of TEAD3 via the Hippo signaling pathway, and this miRNA was associated with poor prognosis. In conclusion, the findings of the present study suggested several underlying miRNA targets for improving the chemotherapy sensitivity of OC.