The profile of microRNA expression and potential role in the regulation of drug-resistant genes in cisplatin and paclitaxel resistant ovarian cancer cell lines
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ABSTRACT:
ORGANISM(S): synthetic construct Homo sapiens
PROVIDER: GSE190245 | GEO | 2022/01/03
REPOSITORIES: GEO
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Project description:Drug resistance poses a major challenge to ovarian cancer treatment. Understanding mechanisms of drug resistance is important for finding new therapeutic targets. In the present work, a cisplatin-resistant ovarian cancer cell line A2780-DR was established with a resistance index of 6.64. The cellular accumulation of cisplatin was significantly reduced in A2780-DR cells as compared to A2780 cells consistent with the general character of drug resistance. Quantitative proteomic analysis identified 340 differentially expressed proteins between A2780 and A2780-DR cells, which involve in diverse cellular processes, including metabolic process, cellular component biogenesis, cellular processes and stress responses. Expression levels of Ras-related proteins Rab 5C and Rab 11B in A2780-DR cells were lower than those in A2780 cells as confirmed by real-time quantitative PCR and western blotting. The short hairpin (sh)RNA-mediated knockdown of Rab 5C in A2780 cells resulted in markedly increased resistance to cisplatin whereas overexpression of Rab 5C in A2780-DR cells increases sensitivity to cisplatin, demonstrating that Rab 5C-dependent endocytosis plays an important role in cisplatin resistance. Our results also showed that expressions of glycolytic enzymes PKM, GPI, Aldolase, LDH, and PGK were down-regulated in drug resistant cells, indicating drug resistance in ovarian cancer is directly associated with a decrease in glycolysis. Furthermore, it was found that glutathione reductase were up-regulated in A2780-DR, while vimentin, HSP90, and Annexin A1 and A2 were down-regulated. Taken together, our results suggest that drug resistance in ovarian cancer cell line A2780 is caused by multifactorial traits, including the down-regulation of Rab 5C-dependent endocytosis of cisplatin, glycolytic enzymes and vimentin, and up-regulation of antioxidant proteins, suggesting Rab 5C is a potential target for treatment of drug-resistant ovarian cancer. This constitutes a further step towards a comprehensive understanding of drug resistance in ovarian cancer.
2016-07-06 | PXD001176 | Pride
Project description:Drug resistance poses a major challenge to ovarian cancer treatment. Understanding mechanisms of drug resistance is important for finding new therapeutic targets. In the present work, a cisplatin-resistant ovarian cancer cell line A2780-DR was established with a resistance index of 6.64. The cellular accumulation of cisplatin was significantly reduced in A2780-DR cells as compared to A2780 cells consistent with the general character of drug resistance. Quantitative proteomic analysis identified 340 differentially expressed proteins between A2780 and A2780-DR cells, which involve in diverse cellular processes, including metabolic process, cellular component biogenesis, cellular processes and stress responses. Expression levels of Ras-related proteins Rab 5C and Rab 11B in A2780-DR cells were lower than those in A2780 cells as confirmed by real-time quantitative PCR and western blotting. The short hairpin (sh)RNA-mediated knockdown of Rab 5C in A2780 cells resulted in markedly increased resistance to cisplatin whereas overexpression of Rab 5C in A2780-DR cells increases sensitivity to cisplatin, demonstrating that Rab 5C-dependent endocytosis plays an important role in cisplatin resistance. Our results also showed that expressions of glycolytic enzymes PKM, GPI, Aldolase, LDH, and PGK were down-regulated in drug resistant cells, indicating drug resistance in ovarian cancer is directly associated with a decrease in glycolysis. Furthermore, it was found that glutathione reductase were up-regulated in A2780-DR, while vimentin, HSP90, and Annexin A1 and A2 were down-regulated. Taken together, our results suggest that drug resistance in ovarian cancer cell line A2780 is caused by multifactorial traits, including the down-regulation of Rab 5C-dependent endocytosis of cisplatin, glycolytic enzymes and vimentin, and up-regulation of antioxidant proteins, suggesting Rab 5C is a potential target for treatment of drug-resistant ovarian cancer. This constitutes a further step towards a comprehensive understanding of drug resistance in ovarian cancer.
2017-03-29 | MSV000080724 | MassIVE
Project description:Cisplatin and carboplatin are the primary first-line therapies for the treatment of ovarian cancer. However, resistance to these platinum-based drugs occurs in the large majority of initially responsive tumors, subsequently resulting in a poor long-term prognosis. To model the onset of drug resistance, we measured gene expression alterations associated with cisplatin resistance. We treated clonally derived, drug-sensitive A2780 epithelial ovarian cancer cells with increasing concentrations of cisplatin. After 5 cycles of drug selection, the isogenic drug-sensitive (parental A2780) and -resistant (Round5 A2780) cell lines were subjected to mRNA expression microarray analyses.
2009-04-17 | E-GEOD-15372 | biostudies-arrayexpress
Project description:Platinum resistance is a major drawback in the treatment of ovarian cancer. Evidence suggests that microRNAs are key players in the initiation, progression, and drug resistance of cancer cells. However, the precise miRNAs dysregulated and contributing to platinum resistance in ovarian cancer cells have not been fully elucidated. Here, we conducted a miRNA expression profiling of cisplatin-sensitive (A2780) and cisplatin-resistant (CP20 and CIS) ovarian cancer cells to identify potential miRNAs involved in platinum resistance.
2020-11-20 | GSE161784 | GEO
Project description:Cisplatin and carboplatin are the primary first-line therapies for the treatment of ovarian cancer. However, resistance to these platinum-based drugs occurs in the large majority of initially responsive tumors, subsequently resulting in a poor long-term prognosis. To model the onset of drug resistance, and investigate the DNA methylation alterations associated with cisplatin resistance, we treated clonally derived, drug-sensitive A2780 epithelial ovarian cancer cells with increasing concentrations of cisplatin. After several cycles of drug selection, the isogenic drug-sensitive and -resistant pairs were subjected to global CGI methylation microarray analyses. We treated clonally derived, drug-sensitive A2780 epithelial ovarian cancer cells with increasing concentrations of cisplatin. After several cycles of drug selection, the isogenic drug-sensitive and -resistant pairs were subjected to global CGI methylation analyses by differential methylation hybridization (DMH) using a customed 44K promoter CGI microarray.
2010-06-19 | E-GEOD-15373 | biostudies-arrayexpress
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
2015-10-14 | GSE73935 | GEO
Project description:Cisplatin and carboplatin are the primary first-line therapies for the treatment of ovarian cancer. However, resistance to these platinum-based drugs occurs in the large majority of initially responsive tumors, subsequently resulting in a poor long-term prognosis. To model the onset of drug resistance, and investigate the DNA methylation alterations associated with cisplatin resistance, we treated clonally derived, drug-sensitive A2780 epithelial ovarian cancer cells with increasing concentrations of cisplatin. After several cycles of drug selection, the isogenic drug-sensitive and -resistant pairs were subjected to global CGI methylation microarray analyses.
2009-04-17 | GSE15373 | GEO
Project description:To investigate the gene targets associated with paclitaxel resistance in EOC, we cultured A2780 and paclitaxel resistant A2780 (A2780-Taxol) cell lines.
2023-06-01 | GSE230667 | GEO
Project description:Cisplatin and other platinum-based drugs are widely used in the treatment of ovarian cancer, but most patients acquire the drug resistance that greatly compromises the efficacy of drugs. Understanding the mechanism of drug resistance is important for finding new therapeutic approaches. In the present study, we found that the expression of vimentin was down-regulated in drug-resistance ovarian cancer A2780-DR and SKOV-3/DDP cells compared to the drug sensitive A2780 and SKOV-3 cells. Overexpression of vimentin in A2780-DR cells markedly increased their sensitivity to cisplatin, whereas knockdown of vimentin in A2780 cells increased the resistance to cisplatin, demonstrating that vimentin plays an important role in cisplatin resistance. Quantitative proteomic analysis identified 95 differentially expressed proteins between A2780-VIM-KN and control cells, which involved in many cellular processes. Down-regulation of endocytic proteins and the up-regulation of exocytic proteins were proposed to contribute the decreased cisplatin accumulation in A2780-VIM-KN cells. Cancer stem cell markers were found to be up-regulated in A2780-VIM-KN cells which were more facile to form spheroids as compared to control cells. Our results also showed that down-regulation of vimentin increased the 14-3-3 mediated retention of Cdc25C in the cytoplasm, leading to inactivation of Cdk1 and the prolonged G2 arrest that allows the longer period of time for cells to repair cisplatin-damaged DNA. Taken together, the down-regulation of vimentin enhances cells’ resistance to cisplatin via mediating multiple cellular processes, suggesting that vimentin is a potential target for treatment of drug resistant ovarian cancer.
2018-10-24 | PXD002825 | Pride
Project description:The development of drug resistance is still a major impediment for the successful treatment of cancer, such as advanced stage ovarian cancer, which has a 5-year survival rate of only 30%. The molecular processes that contribute to resistance have been extensively studied, however, not much is known about the role of microRNAs. We compared microRNA expression profiles of three isogenic cisplatin sensitive and resistant cell line pairs. The only microRNA that was consistently downregulated (FDR = 0.000) in all resistant cell lines was miR-634. We investigated the effects of miR-634 modulation in ovarian cancer cell lines and patient derived tumor cells. Overexpression of miR-634 gave rise to a modest G1 phase block and enhanced apoptosis. Furthermore, miR-634 resensitized resistant ovarian cancer cell lines and patient derived tumor cells to cisplatin chemotherapy. Similarly, miR-634 enhanced the response of tumor cells to carboplatin and doxorubicin, but not to paclitaxel. We showed that miR-634 regulates cyclin D1 (CCND1), which is required for the G1-S phase transition, explaining the effects on the cell cycle. In addition, miR-634 repressed expression of GRB2, ERK2, RSK1 and RSK2, components of the Ras-MAPK pathway. Altogether, our findings suggest that miR-634 modulates several cancer relevant targets and therefore miR-634 is an attractive therapeutic candidate to resensitize chemotherapy resistant ovarian tumors. The miRNA expression profile was determined of three cisplatin sensitive/resistant cell line pairs (ovarian cancer cell line pair A2780/A2780 DDP; colon cancer cell line pair HCT8/HCT8 DDP; bladder cancer cell line pairT24/T24 DDP10).
2014-02-04 | E-GEOD-54665 | biostudies-arrayexpress