The Significance of MicroRNAs Expression in Regulation of Extracellular Matrix and Other Drug Resistant Genes in Drug Resistant Ovarian Cancer Cell Lines

• Published in: International journal of molecular sciences 2020-04, Vol.21 (7), p.2619
• Main Authors: Kazmierczak, Dominika, Jopek, Karol, Sterzynska, Karolina, Ginter-Matuszewska, Barbara, Nowicki, Michal, Rucinski, Marcin, Januchowski, Radoslaw
• Format: Article
• Language: English
• Subjects: ATP Binding Cassette Transporter, Subfamily B - genetics; ATP-binding cassette subfamily B member 1 gene (ABCB1); Cell adhesion & migration; Cell Line, Tumor; Chemotherapy; Cisplatin; Collagen (type III); Collagen Type III - genetics; collagen type III alpha 1 chain gene (COL3A1); DNA microarrays; Doxorubicin; Drug resistance; Drug Resistance, Neoplasm - genetics; Extracellular matrix; Extracellular Matrix - metabolism; Female; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene regulation; Gene Regulatory Networks; Genes; Humans; Immune system; Medical prognosis; microRNA; MicroRNAs; MicroRNAs - genetics; miRNA; Mortality; Ovarian cancer; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Paclitaxel; Proteins; RNA polymerase; Seeds; Topotecan; Transcriptome; Tumor cell lines; Tumors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21072619

Ovarian cancer rates the highest mortality among all gynecological malignancies. 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. Our foremost aim was to exhibit alterations in the miRNA expression levels in cisplatin (CIS), paclitaxel (PAC), doxorubicin (DOX), and topotecan (TOP)-resistant variants of the 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 miRNAs were present. We could observe that, in at least one drug-resistant cell line, the expression of 21 miRNAs was upregulated and that of 19 miRNAs was downregulated. 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 ATP-binding cassette subfamily B member 1 gene ( ) in the paclitaxel-resistant cell line by miR-363 and regulation of the collagen type III alpha 1 chain gene ( ) in the topotekan-resistant cell line by miR-29a.