The significance of microRNA genes expression in ovarian cancer cell lines resistant to cytotoxic drugs

ABSTRACT Ovarian cancer is the most fatal type of gynecological cancer. The main reason for high mortality is the development of drug resistance. It can be related to increased expression of drug transporters and increased expression of extracellular matrix (ECM) proteins. miRNA is a short noncoding RNA that regulates expression of about 60% of genes in the human genome and plays a crucial role in developing cancer, including resistance to chemotherapy. Our foremost aim was to exhibit alterations in the miRNA expression levels in the cisplatin (CIS), paclitaxel (PAC), doxorubicin (DOX), and topotecan (TOP) - resistant variants of W1 sensitive ovarian cancer cell line using miRNA microarray. The second goal was to identify miRNAs responsible for the regulation of drug-resistant genes. According to our observation, alterations in the expression of 40 miRNA genes. The level of expression of 21 genes was upregulated in at least one drug-resistant cell line. The expression of 19 genes was downregulated in at least one drug-resistant cell line. We identified target genes for 22 miRNAs. Target analysis showed that miRNA regulates key genes responsible for drug resistance. Among others, we observed regulation of the ABCB1 (MDR1) gene in the W1PR1 cell line by miR-363 and regulation of the COL3A1 gene in the W1TR cell line by miR-29a. Hence, on the basis of our findings, results indicate that genes responsible for drug resistance development in ovarian cancer can be regulated by miRNA.