Altered microRNA expression in cisplatin-resistant ovarian cancer cells and upregulation of miR-130a associated with MDR1/P-glycoprotein-mediated drug resistance

Abstract

microRNAs (miRNAs) are short non-coding RNA molecules which are involved in the regulation of various biological processes. Drug resistance has become a major obstacle to successful chemotherapy of ovarian cancer. The aim of this study was to investigate microRNA expression profiles in cisplatin-resistant ovarian cancer cells and the role of miR-130a in regulating drug resistance. Analysis of differentially expressed miRNAs between SKOV3 and SKOV3/CIS cells was assessed by miRNA microarrays. Target prediction of miRNAs was determined with the help of PicTar or TargetScan. Among these miRNAs, the expression of miR‑130a was verified using qRT-PCR. The expression of MDR1 mRNA and P-glycoprotein (P-gp) after cellular transfection was examined using qRT-PCR and western blotting, respectively. Cisplatin sensitivity was detected by the MTT assay. We indentified 35 downregulated and 54 upregulated miRNAs in SKOV3/CIS compared to those in SKOV3. We found that miR-130a was upregulated in SKOV3/CIS compared to the parental SKOV3 cells, and PTEN was predicted to be the potential target of miR-130a. Moreover, downregulation of miR-130a could inhibit MDR1 mRNA and P-gp expression and overcome the cisplatin resistance in SKOV3/CIS cells, which indicated that miR-130a may be associated with MDR1/P-gp-mediated drug resistance and plays the role of an intermediate in drug-resistance pathways of PI3K/Akt/PTEN/mTOR and ABC superfamily drug transporters in SKOV3/CIS cells. This study provides important information for the development of targeted gene therapy for reversing cisplatin resistance in ovarian cancer.