Gene expression in HPAECs with ERG and FLI1 knockdown
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE83641 | GEO | 2017/06/22
SECONDARY ACCESSION(S): PRJNA326589
REPOSITORIES: GEO
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Project description:ERG and FLI1 are important regulators of angiogenesis, but their role in lymphatic vasculature is less known. The goal of this study was to determine the role of ERG and FLI1 in postnatal lymphangiogenesis and their involvement in SSc lymphatic system defects. IF were used to detect ERG and FLI1 in SSc and healthy controls (HC) skin biopsies. Human lymphatic endothelial cells (LECs) were used in cell culture experiments. Transcriptional and chromatin analysis of ERG or FLI1 silenced LECs was performed using microarrays and ATAC-seq, respectively. Effects of ERG and FLI1 deficiency on in vitro tubulogenesis was examined using Matrigel assay. Erg and Fli1 endothelial specific knockouts (ErgCKO and Fli1CKO) and lymphatic specific knockouts (ProxErgCKO and ProxFli1CKO) were generated to examine vessel regeneration. ERG and FLI1 protein levels were reduced in blood and lymphatic vasculature in SSc skin biopsies. ERG and FLI1 were shown to regulate genes involved in lymphatic vessel specification, including VEGFR3/FLT4, LYVE-1, and PROX1, and this effect was, at least in part, due to chromatin remodeling. ERG/FLT4 pathway regulated in vitro tubulogenesis in LECs. Deficiency of Erg and Fli1 impaired function of blood and lymphatic vessel during wound healing. ERG and FLI1 are essential regulators of blood and lymphatic vessel regeneration. Deficiency of ERG and FLI1 in SSc endothelial cells, may contribute to rarefaction of blood and lymphatic vasculature in SSc patients. Microarray analysis was performed at The Boston University Microarray Core Facility. Affymetrix CEL files were normalized to produce gene-level expression values using the implementation of the Robust Multiarray Average (RMA) in the affy package (version 1.36.1) included within in the Bioconductor software suite (version 2.12) and an Entrez Gene-specific probe set mapping from BrainArray (version 16.0.0). RLE and NUSE quality metrics were computed using the affy PLM Bioconductor package (version 1.34.0). All microarray analyses were performed using the R environment for statistical computing (version 2.15.1).
2024-05-18 | GSE267348 | GEO
Project description:ERG and FLI1 in endothelial cells
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Project description:EWS-FLI1 is the driver oncogene in >85% of Ewing sarcoma tumors. We used siRNA to knock down EWS-FLI1 for 48h hours in two Ewing sarcoma cell lines (EW8, TC71) to identify downstream genes and pathways affected by loss of EWS-FLI1 activity. RNAseq analysis was performed after 48 hours of treatment with a nontargeting siControl or siEWS-FLI1.
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Project description:To get insight in the functional role of EGR2 for Ewing sarcoma, we performed a transcriptional profiling of Ewing sarcoma cells after knockdown of EGR2 and compared the resulting transcriptional signature with that of EWSR1-FLI1-silenced Ewing sarcoma cells. In accordance with the strong EGR2-induction by EWSR1-FLI1, both genes highly significantly overlap in their transcriptional signatures. Gene-set enrichment analyses (GSEA) and DAVID (Database for Annotation, Visualisation and Integrated Discovery) gene ontology analyses indicated a strong impact of EGR2 on cholesterol and lipid biosynthesis resembling its function in orchestrating lipid metabolism of myelinating Schwann cells. A673 and SK-N-MC Ewing sarcoma cells were transfected with specific siRNAs directed against EGR2 or EWSR1-FLI1 or non-targeting control siRNA. 48 h thereafter RNA was harvested and processed for microarray analysis.
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Project description:Endothelial-to-mesenchymal transition (EndMT) in which endothelial cells lose their characteristics and acquire mesenchymal property has recently been recognized as a driver of disease progression in wide range of pathologies. However, the regulatory mechanism of EndMT has not been fully understood. Here, we found that combined knockdown of two ETS family transcription factors, ERG and FLI1, induced EndMT. Hence, we analyzed functions of ERG and FLI1 using gene expression microarray and ChIP-seq to elucidate the regulatory mechanism of EndMT.
2018-11-23 | GSE109695 | GEO
Project description:: Although vascular dysfunction is a hallmark of chronic aging-associated diseases, including idiopathic pulmonary fibrosis, the role of the pulmonary vasculature to lung repair versus lung fibrosis is not fully understood. We identified the endothelial transcription factor ETS-related gene (ERG) as an orchestrator of vascular homeostasis and repair following lung injury. To evaluate whether loss of endothelial ERG influences the activation of neighboring naïve lung fibroblasts, we collected the conditioned media (CM) generated by control- and ERG-silenced human lung endothelial cells (ECs) and we applied them to normal human lung fibroblasts. We found that CM from ERG-silenced human lung ECs strongly promoted human lung fibroblast activation and enhanced the effect of the fibrogenic mediator TGF. In support of these results, analysis of CM using nanoscale liquid chromatography coupled to tandem mass spectrometry (nano LC-MS/MS) revealed increased secretion of numerous pro-inflammatory and pro-fibrogenic mediators by ERG-silenced human lung ECs in comparison to control-silenced human lung ECs.
2022-06-24 | PXD033847 | Pride
Project description:Gene expression in HPAECs with ERG and FLI1 knockdown
| PRJNA326589 | ENA
Project description:Microarray studies was performed to analyze gene expression profiling in VCaP cells after ERG was silenced by two different siRNAs or VCaP cells were treated by WP1130.
2014-03-03 | GSE53994 | GEO
Project description:To get insight in the functional role of EGR2 for Ewing sarcoma, we performed a transcriptional profiling of Ewing sarcoma cells after knockdown of EGR2 and compared the resulting transcriptional signature with that of EWSR1-FLI1-silenced Ewing sarcoma cells. In accordance with the strong EGR2-induction by EWSR1-FLI1, both genes highly significantly overlap in their transcriptional signatures. Gene-set enrichment analyses (GSEA) and DAVID (Database for Annotation, Visualisation and Integrated Discovery) gene ontology analyses indicated a strong impact of EGR2 on cholesterol and lipid biosynthesis resembling its function in orchestrating lipid metabolism of myelinating Schwann cells.
2015-07-26 | GSE62090 | GEO
Project description:Ewing sarcomas harbor few mutations beyond the chromosomal translocation that initiates disease and the mechanistic basis for the metastasis of these tumors remains poorly understood. The epigenome of Ewing sarcoma (EWS) cells reflects the regulatory state of genes associated with the DNA binding activity of the fusion oncoproteins EWSR1::FLI1 or EWSR1::ERG. In this study, we examined the repressive activities of the EWSR1::FLI1/ERG fusion oncoproteins. Focusing on one of the repressed EWSR1::FLI1/ERG target genes, ETS1, we detected EWSR1::FLI1 binding and a H3K27me3 repressive mark at this locus. Depletion of EWSR1::FLI1 results in ETS1’s binding of promoter regions, and we show ETS1 regulates the expression of multiple proteins that function in extracellular matrix organization including TENSIN3 (TSN3). Interestingly, TSN3 expression in EWS tumors significantly correlates with that of ETS1 (0.85, FDR <0.01). TNS3 is a focal adhesion protein that contributes to tumor cell migration by connecting the cytoplasmic tail of integrins to the actin cytoskeleton. EWS cell lines, in which we activated ETS1 expression (CRISPRa) exhibited increased TNS3 expression and a migratory phenotype. Critically, the activated ETS1 EWS cell lines show TNS3 accumulation at leading cell edges, with F-actin cytoskeletal reorganization, a phenotype associated with cell migration.
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