Knock down of LIMD2 inhibits the invasion and metastasis of ovarian cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE176462 | GEO | 2022/02/09
REPOSITORIES: GEO
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Project description:Knock down of LIMD2 inhibits the invasion and metastasis of ovarian cancer
| PRJNA736333 | ENA
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: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: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:A2780-DR cells are cisplatin resistance compared to A2780. H19 knockdown in A2780-DR cells resulted in recovery of cisplatin sensitivity in vitro and in vivo. To demonstrate how H19 contributes to cisplatin-resistance in ovarian cancer, proteomic analysis was carried out on A2780, A2780-DR, A2780-DR/H19si, and A2780-DR/control cells. Proteins expression levels were identified and quantified using MaxQuant software (http://medusa.biochem.mpg.de/maxquant_doku/). The experiments were repeated twice and the false-positive rate was set to be <1%. Based on label-free quantification intensity ratios (>1.67 or <0.6) in proteins that have two or more unique peptides.
2018-10-25 | PXD003252 | Pride
Project description:To determine the signaling networks that are dysregulated in platinum-resistant ovarian cancer, gene expression data were obtained from, and compared between, the ovarian cancer cell line, A2780, and its cisplatin-resistant derivative, A2780cis. Gene expression data from a cisplatin-sensitive ovarian cancer cell line (A2780) were collected and compared to gene expression data from a cisplatin-resistant cell line (A2780cis). 6 independent experiments were completed for both the sensitive and resistant cell lines.
2011-11-05 | E-GEOD-33482 | biostudies-arrayexpress
Project description:A2780 is a cisplatin sensitive ovarian cancer cell line. A2780 ovarian cancer cells was treated with different doses of cisplatin in an attempt to identify biomarkers that can be used to predict chemoresponse. We used microarrays to identify genes induced by cisplatin in a time dependent manner.
2018-11-08 | GSE122287 | GEO
Project description:The high-throughput sequencing technology was performed after the treatment of human ovarian cancer cells A2780 with TMPyP4 and H2O2 purchased from Sigma-Aldrich, to explore the expression of genes related to cell proliferation, DNA damage and ROS levels of ovarian cancer cells A2780 after the treatment of TMPyP4 and H2O2, and to find an interesting target pathway,HIF-1 signaling pathway.
2024-03-25 | GSE262015 | GEO
Project description:To investigate the main mechanism underlying cisplatin resistance in ovarian cancer, A2780/CDDP and SKOV3/CDDP cell lines were treated with both maggot extracts and cisplatin. We then performed gene expression profiling analysis using data obtained from RNA-seq of A2780 and A2780/CDDP cells.
2022-06-25 | GSE206649 | GEO
Project description:We have previously shown that SUM-149 human breast cancer cells require an amphiregulin (AREG) autocrine loop for cell proliferation. We also demonstrated that AREG can increase epidermal growth factor receptor (EGFR) stability and promote EGFR localization to the plasma membrane. In the present studies we successfully knocked-down AREG expression in SUM-149 cells by lentiviral infection of AREG shRNA. In the absence of AREG expression, SUM-149 cell growth was slowed, but not completely inhibited. Furthermore, cells infected with AREG shRNA constructs showed an increase in EGFR protein expression by Western blot. Immunofluorescence and confocal microscopy showed that following AREG knock-down, EGFR continued to localize to the cell surface. Soft agar assays demonstrated that AREG knock-down cells retain anchorage-independent growth capacity. Additionally mammosphere forming assays and Adefluor staining analysis showed that knock-down of AREG expression did not affect the expression of stem cell phenotypes. However, following AREG knock-down, SUM-149 cells demonstrated a dramatic decrease in their ability to invade a Matrigel matrix. Consistent with this observation, microarray analysis comparing cells infected with a non-silencing vector to the AREG knock-down cells, identified genes associated with the invasive phenotype such as RHOB and DKK1, and networks associated with cell motility such as integrin-linked kinase signaling, and focal adhesion kinase signaling. AREG was also found to modulate WNT and Notch signaling in these cells. Thus, AREG functions in regulating the invasive phenotype, and we propose that this regulation may be through altered signaling that occurs when AREG activates plasma membrane localized EGFR.
| S-EPMC3865809 | biostudies-literature