Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA188671 | ENA |
REPOSITORIES: ENA
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Project description:Biomarkers that predict disease progression might assist the development of better therapeutic strategies for aggressive cancers, such as ovarian cancer. Here, we investigated the role of collagen type XI alpha 1 (COL11A1) in cell invasiveness and tumor formation and the prognostic impact of COL11A1 expression in ovarian cancer. Microarray analysis suggested that COL11A1 is a disease progression-associated gene that is linked to ovarian cancer recurrence and poor survival.
2014-01-01 | GSE44104 | GEO
Project description:Biomarkers that predict disease progression might assist the development of better therapeutic strategies for aggressive cancers, such as ovarian cancer. Here, we investigated the role of collagen type XI alpha 1 (COL11A1) in cell invasiveness and tumor formation and the prognostic impact of COL11A1 expression in ovarian cancer. Microarray analysis suggested that COL11A1 is a disease progression-associated gene that is linked to ovarian cancer recurrence and poor survival. Whole tumor gene expression profiling was conducted on tissue samples from 60 ovarian cancer patients, and characteristics and clinico-pathological features of the patients are provided. We used several steps to analyze the expression profiles of the samples to identify the genes whose expression values correlate with survival, recurrence and advanced disease stage. First, using hazard ratios from univariate Cox regression analysis, the top 200 survival-related genes were evaluated for intersection with the top 200 recurrence-related genes, and 44 genes were obtained. Second, we examined the 44 genes that met the criteria of fold-change values between advanced stage and early stage samples of greater than 2 or less than 0.5. Ultimately, 17 genes were identified. A heat map of the 17 genes is depicted in the associated publication. Gene ontology and pathway enrichment analyses of the 17 genes were performed using Database for Annotation, Visualization and Integrated Discovery (DAVID). The major cellular component, biological process and molecular function of the 17 genes are associated with the extracellular region, intracellular signaling cascade, and protein binding and bridging, respectively. Two genes, COL11A1 and COL4A6, are involved in ECM-receptor interaction pathways. Notably, COL11A1 displayed the highest fold-change value in ovarian cancer disease progression; therefore, we selected COL11A1 for further experimental analysis.
2014-01-01 | E-GEOD-44104 | biostudies-arrayexpress
Project description:Collagen type XI alpha 1 (COL11A1) is identified as one of the most upregulated genes in cisplatin-resistant ovarian cancer and recurrent ovarian cancer. However, the exact functions of COL11A1 in cisplatin resistance are unknown. The goal of this study is to determine molecular mechanisms by which COL11A1 confers cisplatin resistance in ovarian cancer cells. We overexpressed COL11A1 in A2780 and OVCAR3 ovarian cancer cells, which express very low endogenous levels of COL11A1. We then compared the mRNA expression levels of various genes between COL11A1-overexpressing ovarian cancer cells and control ovarian cancer cells by RNA-Seq. Our RNA-Seq data show that COL11A1 overexpression did not consistently change the expression levels of genes involved in cisplatin efflux, glutathione metabolism, and DNA repair pathways, which are known to contribute to cisplatin resistance. This result implies that COL11A1 might confer cisplatin resistance in ovarian cancer cells through other mechanisms.
2019-10-10 | GSE112985 | GEO
Project description:We have identified the overexpression of FGF18 as an independent predictive marker for poor clinical outcome in patients with advanced stage, high-grade serous ovarian cancer. Functional studies have demonstrated that FGF18 promotes migration, invasion and tumorigenicity of ovarian cancer cells in vitro and in vivo. To identify the FGF18 responsive genes contributing its biologic effects on ovarian tumorigenesis, we performed gene expression profiling in ovarian cancer cell line A224 with ectopic overexpression of FGF18 or RFP (as control). Microarrays were completed using total genomic DNA free RNA extracted from three independent paired cultures of A224 cells overexpressing FGF18 or RFP.
2013-07-08 | E-GEOD-48567 | biostudies-arrayexpress
Project description:While VEGF-targeted therapies are showing promise in clinical studies, new angiogenesis targets are needed to make additional gains. Here, we show that increased Zeste homologue 2 (EZH2) expression in either tumor cells or in tumor vasculature is predictive of poor clinical outcome. The increase in endothelial EZH2 is a direct result of VEGF stimulation and indicates the presence of a paracrine circuit that promotes angiogenesis by methylating and silencing vasohibin 1 (VASH1). EZH2 silencing in the tumor-associated endothelial cells resulted in inhibition of angiogenesis mediated by reactivation of VASH1, and reduced ovarian cancer growth. Combined, these data provide a new understanding of the regulation of tumor angiogenesis and support the potential for targeting EZH2 as a novel therapeutic approach. Pre-clinical study, DNA microarray (Illumina HumanHT-12)
2010-10-12 | E-GEOD-20381 | biostudies-arrayexpress
Project description:Collagen type XI alpha 1 (COL11A1) is a novel biomarker associated with cisplatin resistance in ovarian cancer. However, the mechanisms underlying how COL11A1 confers cisplatin resistance in ovarian cancer are poorly understood. We identified that fatty acid β-oxidation (FAO) is upregulated by COL11A1 in ovarian cancer cells and that COL11A1-driven cisplatin resistance can be abrogated by inhibition of FAO. Furthermore, our results demonstrate that COL11A1 also enhances the expression of proteins involved in fatty acid synthesis. Interestingly, COL11A1-induced upregulation of fatty acid synthesis and FAO is modulated by the same signaling molecules. We identified that binding of COL11A1 to its receptors, α1β1 integrin and discoidin domain receptor 2 (DDR2), activates Src-Akt-AMPK signaling to increase the expression of both fatty acid synthesis and oxidation enzymes, although DDR2 seems to be the predominant receptor. Inhibition of fatty acid synthesis downregulates FAO despite the presence of COL11A1, suggesting that fatty acid synthesis might be a driver of FAO in ovarian cancer cells. Taken together, our results suggest that COL11A1 upregulates fatty acid metabolism in ovarian cancer cells in a DDR2-Src-Akt-AMPK dependent manner. Therefore, we propose that blocking FAO might serve as a promising therapeutic target to treat ovarian cancer, particularly cisplatin-resistant recurrent ovarian cancers which typically express high levels of COL11A1.
2020-04-28 | PXD016244 | Pride
Project description:We have identified the overexpression of FGF18 as an independent predictive marker for poor clinical outcome in patients with advanced stage, high-grade serous ovarian cancer. Functional studies have demonstrated that FGF18 promotes migration, invasion and tumorigenicity of ovarian cancer cells in vitro and in vivo. To identify the FGF18 responsive genes contributing its biologic effects on ovarian tumorigenesis, we performed gene expression profiling in ovarian cancer cell line A224 with ectopic overexpression of FGF18 or RFP (as control).
2013-07-08 | GSE48567 | GEO
Project description:Epithelial ovarian carcinoma (EOC) is an aggressive tumor often diagnosed at an advanced stage, when there is little prospect for cure. Despite some advances in surgical and chemotherapeutic strategies, only marginal improvements in patient outcome have been obtained. Hence, understanding the biological mechanisms underpinning EOC progression is critical for its treatment and to ameliorate patients survival. Recently, we reported that CD157 is expressed in EOC and controls tumor cell migration and invasion. Using stable overexpression and knockdown in OVCAR-3 and OV-90 ovarian cancer cell lines, we demonstrated that CD157 overexpression promotes morphological and functional changes, characterized by downregulation of epithelial marker and upregulation of mesenchymal ones. These are mediated at the transcriptional level by altering the expression of Snail and Zeb1 transcriptional repressors. The effects of CD157 overexpression on ovarian cancer phenotype translate into increased tumor cell motility and mesotelial invasion, while its knockdown significantly reduces the migratory potential, implying a direct correlation between CD157 expression levels and EOC aggressiveness. The analysis of the transcriptomic profiling highlighted 378 significantly differentially expressed genes, representing the signature of CD157-overexpressing EOC cells. The overall picture deduced from the analysis of these modulated transcripts indicated that high CD157 expression results in strengthening of a number of biological functions that favour tumor progression (including cell differentiation, cell motility and migration), and weakening of selected biological processes that hinder the tumor progression (such as apoptosis, cell death and response to stress). Collectively, these data support a causal role of CD157 in the control of ovarian cancer progression motivating the existence of a direct correlation between the expression levels of CD157 and the adverse clinical outcome in EOC patients, and suggest that CD157 may represent a valuable therapeutic target. Gene expression analysisi of control cell lines (OVCAR-3/mock and OV-90/mock) and testing cell lines (OVCAR-3/CD157 and OV-90/CD157), with two replicates, with dye swap, performed for each sample.
2012-12-31 | E-GEOD-36364 | biostudies-arrayexpress
Project description:While VEGF-targeted therapies are showing promise in clinical studies, new angiogenesis targets are needed to make additional gains. Here, we show that increased Zeste homologue 2 (EZH2) expression in either tumor cells or in tumor vasculature is predictive of poor clinical outcome. The increase in endothelial EZH2 is a direct result of VEGF stimulation and indicates the presence of a paracrine circuit that promotes angiogenesis by methylating and silencing vasohibin 1 (VASH1). EZH2 silencing in the tumor-associated endothelial cells resulted in inhibition of angiogenesis mediated by reactivation of VASH1, and reduced ovarian cancer growth. Combined, these data provide a new understanding of the regulation of tumor angiogenesis and support the potential for targeting EZH2 as a novel therapeutic approach.
2010-10-12 | GSE20381 | GEO
Project description:Mitochondria are dynamic organelles that are important for cell growth and proliferation. Dysregulated mitochondrial dynamics are highly associated with the initiation and progression of various cancers, including ovarian cancer. However, the regulatory mechanism underlying mitochondrial dynamics is still not fully understood. Previously, our study showed that carnitine palmitoyltransferase 1A (CPT1A) is highly expressed in ovarian cancer cells and promotes the development of ovarian cancer. Here, we find that CPT1A regulates mitochondrial dynamics and promotes mitochondrial fission in ovarian cancer cells. Our study futher shows that CPT1A regulates mitochondrial fission and function through mitochondrial fission factor (MFF) to promote the growth and proliferation of ovarian cancer cells. Mechanistically, we show that CPT1A promotes succinylation of MFF at lysine 302 (K302), which protects against Parkin-mediated ubiquitin-proteasomal degradation of MFF. Finally, the study shows that MFF is highly expressed in ovarian cancer cells and that high MFF expression is associated with poor prognosis in patients with ovarian cancer. MFF inhibition significantly inhibits the progression of ovarian cancer in vivo. Overall, CPT1A regulates mitochondrial dynamics through MFF succinylation to promote the development of ovarian cancer. Moreover, our findings suggest that MFF is a potential therapeutic target for ovarian cancer.
2023-05-15 | PXD041990 | Pride