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MicroRNA profiling in resistance ovarian cell lines

ABSTRACT: Although many genes associated with the development of resistance to chemotherapy are known, the mechanisms of their regulation are still poorly understood. One of the ways to regulate gene expression is regulation at mRNA level by small noncoding RNA particles – designated as a micro RNA (miRNA). Changes in miRNA expression were also observed in cell line studyes. Downregulation of miR-31 expression correlated with taxane resistance in ovarian cancer cell lines. In contrast upregulation of miR-98-5p was observed in cisplatin (CIS) -resistant cell lines. Changes in miRNAs expression were also noted in another cancers. miR-195 expression was downregulated in temozolomid-resistant glioma cells and miR-203 was downregulated in prostate cancer cells resistant to doxorubicin (DOX). The use of miRNA microarrays to analyse changes in miRNA gene expression is an effective molecular tool for the discovering new miRNA genes involved in drug resistance processes. The present study shows alterations in the miRNA expression levels in the CIS (W1CR), PAC (W1PR1 and W1PR2), DOX (W1DR), and topotecan (TOP) (W1TR) - resistant variants of W1 sensitive ovarian cancer cell line.

ORGANISM(S): synthetic construct Homo sapiens

PROVIDER: GSE148251 | GEO | 2020/04/08

REPOSITORIES: GEO

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Project description:The development of cytostatic-drug resistance renders chemotherapy ineffective in treating ovarian cancer, the most lethal gynaecological malignancy. In many cases, it is difficult to explain the development of drug resistance based on the expression patterns of genes known to be involved in this process. Microarray-based assays can provide information about new genes that are involved in the resistance to cytostatic drugs. This report describes alterations in the level of expression of genes in cisplatin- (CisPt), doxorubicin- (Dox), topotecan- (Top), and paclitaxel- (Pac) resistant variants of W1 and A2780 ovarian cancer cell lines. These drug-resistant variants of the W1 and A2780 cell lines were generated through the stepwise selection of cells tolerant of exposure to the indicated drugs at incrementally increased concentrations. Affymetrix GeneChip Human Genome Array Strips were used for hybridization assays. The genes with significantly altered expression levels (upregulated by more than fivefold or downregulated by less than fivefold relative to the level in the parental line) in the drug-resistant sublines were selected and were filtered using volcano plotting. We observed alterations in the expression of 22 genes that were common to all three cell lines that were resistant to the same cytostatic drug. The level of expression of 13 genes was upregulated and that of nine genes was downregulated. In the CisPt-resistant cell line, we observed downregulated expression of ABCC6, BST2, ERAP2 and MCTP1; in the Pac-resistant cell line, we observe upregulated expression of ABCB1, EPHA7 and RUNDC3B and downregulated expression of LIPG, MCTP1, NSBP1, PCDH9, PTPRK and SEMA3A. The expression levels of three genes, ABCB1, ABCB4 and IFI16, were upregulated in the Dox-resistant cell lines. In the Top-resistant cell lines, we observed increased expression levels of ABCG2, HERC5, IFIH1, MYOT, S100A3, SAMD4A, SPP1 and TGFBI and decreased expression levels of MCTP1 and PTPRK

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MicroRNA profiling in resistance ovarian cell lines

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