Ewing sarcoma compared to a normal body map
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Olivia Prazeres da Costa
PROVIDER: E-GEOD-45544 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Primary pediatric Ewing sarcoma (ES), one uncharacterized sarcoma as well as primary and well established ES cell lines were compared to probes of different normal tissues
2013-11-01 | GSE45544 | GEO
Project description:The Ewing Sarcoma cell lines A673, SK-ES-1, and SK-N-MC were treated with without 5-AZA to identify upregulated genes A673, SK-ES-1, and SK-N-MC were treated with 5-AZA
2012-09-01 | E-GEOD-36858 | biostudies-arrayexpress
Project description:The Ewing Sarcoma cell lines A673, SK-ES-1, and SK-N-MC were treated with without 5-AZA to identify upregulated genes
2012-09-01 | GSE36858 | GEO
Project description:Transcriptomic analysis of the well-characterized Ewing sarcoma cell line A673 indicated that one of the genes more strongly upregulated by EWSR1-FLI1 was FEZF1 (FEZ family zinc finger protein 1), a transcriptional repressor involved in brain development and neural cell identity. FEZF1 was highly expressed in Ewing sarcoma cells but not in other bone tumors such as osteosarcoma or chondrosarcoma. FEZF1 promoter contains a large GGAA-microsatellite and the number of GGAA repeats correlated positively with FEZF1 expression levels in Ewing sarcoma cell lines. To characterize the functional role of FEZF1 in Ewing sarcoma we analyzed the effect of FEZF1 knockdown in three Ewing sarcoma cell lines (A673, SKNMC, SKES1). FEZF1 knockdown inhibited clone formation in clonogenic assays and cell proliferation. Finally, we analyzed the FEZF1-dependent expression profile in A673 cells by RNAseq. Interestingly, several neural genes regulated by FEZF1 were concomitantly regulated by EWSR1-FLI1. In summary, FEZF1 is a transcriptional target of EWSR1-FLI1 in Ewing sarcoma cells involved in the regulation of neural-specific genes which could explain, at least in part, the neural-like phenotype observed in several Ewing sarcoma tumors and derived cell lines.
2021-11-22 | GSE184679 | GEO
Project description:We show that EWS-FLI1, an aberrant transcription factor responsible for the pathogenesis of Ewing sarcoma, reprograms gene regulatory circuits by directly inducing or directly repressing enhancers. At GGAA repeats, which lack regulatory potential in other cell types and are not evolutionarily conserved, EWS- FLI1 multimers potently induce chromatin opening, recruit p300 and WDR5, and create de novo enhancers. GGAA repeat enhancers can loop to physically interact with target promoters, as demonstrated by chromosome conformation capture assays. Conversely, EWS-FLI1 inactivates conserved enhancers containing canonical ETS motifs by displacing wild-type ETS transcription factors and abrogating p300 recruitment. ChIP-seq for of 4 histone modifications (H3K27ac, H3K4me1, H3K4me3 and H3K27me3), FLI1, p300, WDR5, ELF1 and GABPA in primary Ewing sarcomas, Ewing sarcoma cell lines (A673 and SKMNC cells), and mesenchymal stem cells (MSC). EWS-FLI1 was knocked down in Ewing sarcoma cell lines with lentiviral shRNAs (shFLI1 and shGFP control). EWS-FLI1 was expressed in MSCs with lentiviral expression vectors (pLIV EWSFLI1 or pLIV empty vector control). * Raw data not provided for the MSC and Primary Ewing sarcoma samples. *
2014-10-30 | E-GEOD-61944 | biostudies-arrayexpress
Project description:An increasing number of cancer-associated mutations have been identified. Unfortunately, little therapy today exploits these tumor-specific genetic lesions. Often, the resulting oncoproteins have been intractable to easy manipulation with current small molecule screening approaches. To overcome this impasse, we developed an expression-based approach to small molecule library screening. We applied this platform to the discovery of modulators of the activity of EWS/FLI, the Ewing sarcoma associated oncoprotein. Cytarabine (ARA-C) was identified as the top hit in a small molecule library screen. ARA-C modulates EWS/FLI by decreasing EWS/FLI protein level and has striking effects on cellular viability and transformation in in vitro and in vivo models of Ewing sarcoma. With poor outcomes for patients with relapsed Ewing sarcoma and the well established safety profile of ARA-C, clinical trials testing ARA-C in Ewing sarcoma are warranted. Expression data was created for A673 cells treated with ARA-C and two other compounds used to treat Ewing sarcoma (Puromycin and Doxorubicin) at two doses (EC50 and 2xEC50) and three time points (24 hours, 3 days, and 5 days). Experiment Overall Design: A673 cells were treated with ARA-C (at doses of EC50 and 2xEC50) or vehicle in triplicate and expression profiled at 24 hours, 3 days, and 5 days. To exclude the possibility that ARA-C's modulation of the EWS/FLI signature was simply a non-specific response to treatment with all cytotoxic agents, we asked whether other compounds known to kill Ewing sarcoma cells (Doxorubicin and Puromycin) would induce the EWS/FLI off genome-wide expression pattern. A673 cells were treated with Doxorubicin and Puromycin (at doses of EC50 and 2xEC50) and expression profiled at 24 hours, 3 days, and 5 days.
2008-11-22 | E-GEOD-6930 | biostudies-arrayexpress
Project description:EWS-FLI-1 was silenced by an shRNA in A673 Ewing sarcoma cells and the resulting alterations in the secretome was analyzed by GeLC-MS/MS approach (six gel slices for each sample, luciferase shRNA-expressing cell secretome as control)
2021-07-06 | PXD016052 | Pride
Project description:The expression profile of primary pediatric Ewing sarcoma (ES) and osteosarcoma (OS) were analyzed. 8 Ewing sarcoma patient samples (TUM-ES0XXX) and 10 osteosarcoma patient samples (TUM-OS0XXX) were analyzed.
2016-07-05 | E-GEOD-73166 | biostudies-arrayexpress
Project description:Ewing sarcoma is an aggressive pediatric small round cell tumor that predominantly occurs in bone. Approximately 85% of Ewing sarcomas harbor the EWS/FLI fusion protein, which arises from a chromosomal translocation, t(11:22)(q24:q12). EWS/FLI interacts with numerous lineage-essential transcription factors to maintain mesenchymal progenitors in an undifferentiated state. We previously showed that EWS/FLI binds the osteogenic transcription factor RUNX2 and prevents osteoblast differentiation. In this study, we investigated the role of another Runt-domain protein, RUNX3, in Ewing sarcoma. RUNX3 participates in mesenchymal-derived bone formation and is a context dependent tumor suppressor and oncogene. RUNX3 was detected in all Ewing sarcoma cells examined, whereas RUNX2 was detected in only 73% of specimens. Like RUNX2, RUNX3 binds to EWS/FLI via its Runt domain. EWS/FLI prevented RUNX3 from activating the transcription of a RUNX-responsive reporter, p6OSE2. Stable suppression of RUNX3 expression in the Ewing sarcoma cell line A673 delayed colony growth in anchorage independent soft agar assays and reversed expression of EWS/FLI-responsive genes. These results demonstrate an important role for RUNX3 in Ewing sarcoma. RNA-seq to compare transcriptiome of control A673 ewing sarcoma cells stably expression a non-target or RUNX3 shRNA
2014-05-01 | E-GEOD-56900 | biostudies-arrayexpress
Project description:Ewing sarcomas (ES) are highly malignant, osteolytic bone or soft tissue tumors, which are characterized by early metastasis into lung and bone. Genetically, ES are defined by balanced chromosomal EWS/ETS translocations, which give rise to chimeric proteins (EWS-ETS) that generate an oncogenic transcriptional program associated with altered epigenetic marks throughout the genome. By use of an inhibitor (JQ1) blocking BET bromodomain binding proteins (BRDs) we strikingly observed a strong down-regulation of the predominant EWS-ETS protein EWS/FLI1 in a dose dependent manner. Microarray analysis further revealed JQ1 treatment to block a typical ES associated expression program. The effect on this expression program could be mimicked by RNA interference with BRD3 or BRD4 expression, indicating that the EWS/FLI1 mediated expression profile is at least in part mediated via such epigenetic readers. Consequently, contact dependent and independent proliferation of different ES lines was strongly inhibited. Mechanistically, treatment of ES resulted in a partial arrest of the cell cycle as well as induction of apoptosis. Tumor development was suppressed dose dependently in a xeno-transplant model in immune deficient mice, overall indicating that ES may be susceptible to treatment with epigenetic inhibitors blocking BET bromodomain activity and the associated pathognomonic EWS-ETS transcriptional program in ES. Ewing sarcoma cell lines A673 and TC-71 were treated for 48 hours with 2 microM JQ1 or DMSO control.
2015-12-08 | E-GEOD-72673 | biostudies-arrayexpress