Expression and functional pathway analysis of nuclear receptor NR2F2 in Ovarian cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE47438 | GEO | 2013/05/29
SECONDARY ACCESSION(S): PRJNA205562
REPOSITORIES: GEO
Similar Datasets
Project description:Analysis of NR2F2 knockdown at whole genome level Total RNA isolated 48 hours after NR2F2 knockdown with siRNA compared to siRNA with non-targeting control
2013-05-29 | E-GEOD-47438 | biostudies-arrayexpress
Project description: Not available
| S-EPMC3701283 | biostudies-literature
Project description:Gene expression profiles of primary lymphatic endothelial cells (LECs) isolated from human foreskin were analyzed after siRNA-mediated knockdown of control (firefly luciferase), Prox1, NR2F2 or Prox1/NR2F2 for 48 hours. Experiment Overall Design: Passage five human lymphatic endothelial cells (LECs) were cultured on fibronectin (10 μg/ml)-coated plates in a complete media (EBM, 20% FBS supplemented with 10 μg/ml hydrocortisone acetate, 25 ug/ml cAMP and antibiotics). LECs were harvested and electorporated with siRNA duplexes for 48 hours with siRNA duplexes against either firefly luciferase(control), Prox1, NR2F2 or Prox1/NR2F2. Total RNA was purified using Tri-reagent and was subjected to microarray analysis. Experiment Overall Design:
2008-10-25 | E-GEOD-12846 | biostudies-arrayexpress
Project description:NF1 loss-of-function mutations are enriched in hormone receptor positive (HR+) metastatic breast cancer (MBC) and mediate endocrine therapy resistance. To identify therapeutic vulnerabilities in this context, we performed CRISPR/Cas9 screens in wildtype and NF1 knockout isogenic HR+ models and identified NR2F2, an orphan nuclear receptor, to be essential specifically in NF1 loss cells. The NR2F2 dependence was induced as a consequence of NR2F2 upregulation via the activation of the MAPK pathway in these cells. Enforced overexpression of NR2F2 was sufficient to confer endocrine therapy resistance in the absence of NF1 loss, while of NR2F2 knockout or knockdown could enhance the efficacy of endocrine therapies in NF1 WT and NF1 loss models. Mechanistically, our comprehensive multi-omics approaches revealed that NR2F2 modulates chromatin accessibility and regulates ER-dependent transcription through its interaction with ER, transcriptional coregulators and chromatin remodelers at chromatin. Specifically, increased NR2F2 in NF1 loss cells dramatically enhanced the association with transcriptional corepressors, which resulted in attenuation of chromatin accessibility and ER occupancy, and impaired ER transcriptional program. Our findings identify the nuclear receptor NR2F2 as a downstream effector of NF1 loss, and it is essential and potentially druggable mediator of endocrine therapy resistance. We performed chromatin accessibility profiling analysis using data obtained from ATAC-seq of MCF7 sgNT, sgNF1, sgNR2F2 and double knockout (DKO) cells.
2022-11-10 | GSE217415 | GEO
Project description:NF1 loss-of-function mutations are enriched in hormone receptor positive (HR+) metastatic breast cancer (MBC) and mediate endocrine therapy resistance. To identify therapeutic vulnerabilities in this context, we performed CRISPR/Cas9 screens in wildtype and NF1 knockout isogenic HR+ models and identified NR2F2, an orphan nuclear receptor, to be essential specifically in NF1 loss cells. The NR2F2 dependence was induced as a consequence of NR2F2 upregulation via the activation of the MAPK pathway in these cells. Enforced overexpression of NR2F2 was sufficient to confer endocrine therapy resistance in the absence of NF1 loss, while of NR2F2 knockout or knockdown could enhance the efficacy of endocrine therapies in NF1 WT and NF1 loss models. Mechanistically, our comprehensive multi-omics approaches revealed that NR2F2 modulates chromatin accessibility and regulates ER-dependent transcription through its interaction with ER, transcriptional coregulators and chromatin remodelers at chromatin. Specifically, increased NR2F2 in NF1 loss cells dramatically enhanced the association with transcriptional corepressors, which resulted in attenuation of chromatin accessibility and ER occupancy, and impaired ER transcriptional program. Our findings identify the nuclear receptor NR2F2 as a downstream effector of NF1 loss, and it is essential and potentially druggable mediator of endocrine therapy resistance. We performed gene expression profiling analysis using data obtained from RNA-seq of MCF7 sgNT, sgNF1, sgNR2F2 and double knockout (DKO) cells under different conditions.
2023-06-08 | GSE234074 | GEO
Project description:NF1 loss-of-function mutations are enriched in hormone receptor positive (HR+) metastatic breast cancer (MBC) and mediate endocrine therapy resistance. To identify therapeutic vulnerabilities in this context, we performed CRISPR/Cas9 screens in wildtype and NF1 knockout isogenic HR+ models and identified NR2F2, an orphan nuclear receptor, to be essential specifically in NF1 loss cells. The NR2F2 dependence was induced as a consequence of NR2F2 upregulation via the activation of the MAPK pathway in these cells. Enforced overexpression of NR2F2 was sufficient to confer endocrine therapy resistance in the absence of NF1 loss, while of NR2F2 knockout or knockdown could enhance the efficacy of endocrine therapies in NF1 WT and NF1 loss models. Mechanistically, our comprehensive multi-omics approaches revealed that NR2F2 modulates chromatin accessibility and regulates ER-dependent transcription through its interaction with ER, transcriptional coregulators and chromatin remodelers at chromatin. Specifically, increased NR2F2 in NF1 loss cells dramatically enhanced the association with transcriptional corepressors, which resulted in attenuation of chromatin accessibility and ER occupancy, and impaired ER transcriptional program. Our findings identify the nuclear receptor NR2F2 as a downstream effector of NF1 loss, and it is essential and potentially druggable mediator of endocrine therapy resistance. We performed ER chromatin binding profiling analysis using data obtained from ChIP-seq of MCF7 sgNT, sgNF1, sgNR2F2 and double knockout (DKO) cells under the conditions of full media, estrogen starvation and estrogen stimulation. We also performed NR2F chromatin binding profiling analysis using data obtained from ChIP-seq of MCF7 sgNT and sgNF1 cells under full media culture condition
2022-11-10 | GSE217416 | GEO
Project description:Gene expression profiles of primary lymphatic endothelial cells (LECs) isolated from human foreskin were analyzed after siRNA-mediated knockdown of control (firefly luciferase), Prox1, NR2F2 or Prox1/NR2F2 for 48 hours.
2008-09-20 | GSE12846 | GEO
Project description:We show that most binding events of NR2F2 occur together with the ERα binding sites.To address the functional relationship between NR2F2 and ERα, we assessed the role of NR2F2 in oestrogen-induced growth in ER positive cell line MCF-7. The MTT experiment showed that inhibition of NR2F2 prevented the oestrogen-induced proliferation of MCF-7 cells.To further explore the effect of NR2F2 on estrogen response, We expanded our knockdown studies by performing RNA-seq analysis for MCF-7 cells transfected with control or NR2F2 shRNAs with or without E2.
2019-10-15 | GSE132433 | GEO
Project description:Orphan nuclear receptor chicken ovalbumin upstream promoter transcription factor 2 (COUPTF2; NR2F2) is highly expressed in endothelial cells (ECs) and Nr2f2 knockout produces lethal cardiovascular defects. In humans, NR2F2 mutations result in both congenital heart disease and diaphragmatic hernia, conditions associated with the development of pulmonary arterial hypertension (PAH). However, COUPTF2 functions in mature endothelium are uncertain. NR2F2 knockdown in primary human endothelial cells (ECs) led to an interferon-biased inflammatory response, endothelial-to-mesenchymal transition, proliferation, hypermigration, apoptosis-resistance and mitochondrial dysfunction. These phenotypic changes were associated with AKT activation and increased Dickkopf-1 (DKK1) expression, a Wnt/β-catenin pathway inhibitor. DKK1 was also elevated in patients with PAH and secreted in response to loss of bone morphogenetic receptor type 2 (BMPR2), the archetypal PAH-associated genetic defect. Together, these findings demonstrate that endothelial NR2F2 suppresses inflammation and proliferation. Thus, NR2F2 loss disrupts EC homeostasis and may promote pathologic vascular remodeling in the development of PAH.
2023-05-31 | GSE188465 | GEO