Similar Datasets
Project description:The mechanisms underlying tumor cell plasticity driving drug resistance and disease progression remain poorly understood. In Ewing sarcoma (EwS), variations in EWS::FLI1 (EF) activity have been associated with epithelial-mesenchymal plasticity (EMP). Using degron technology, we titrated endogenous EF in an EwS cell line and linked phenotypic states to distinct EF thresholds. Strikingly, modest EF depletion promoted a pro-metastatic phenotype, which was diminished upon near-complete EF loss. Transcriptomic analysis revealed distinct gene clusters with heterogenous response patterns to varying EF dosage. Target genes most sensitive to subtle EF depletion contained GGAA microsatellites in EF-bound enhancers. Furthermore, we identified Krüppel-like zinc-finger transcription factors to be associated with EF-repressed EMP genes. EF rescue after partial depletion for a transient period identified persistently dysregulated genes associated with poor prognosis. This study underscores the therapeutic challenge of insufficient EF inhibition and provides a foundation for exploiting oncoprotein dynamics to uncover therapeutic vulnerabilities in fusion-driven cancers.
2025-04-10 | GSE291134 | GEO
Project description:A major maturity duration-regulatory gene, Early flowering-completely dominant (Ef-cd) was cloning in this study. The Ef-cd locus gives rise to a long noncoding RNA (lncRNA) antisense transcript overlapping the OsSOC1 gene. Ef-cd lncRNA expression positively correlates with the expression of OsSOC1 and H3K36me3 deposition.
2019-07-10 | GSE134021 | GEO
Project description:The mechanisms underlying tumor cell plasticity driving drug resistance and disease progression remain poorly understood. In Ewing sarcoma (EwS), variations in EWS::FLI1 (EF) activity have been associated with epithelial-mesenchymal plasticity (EMP). Using degron technology, we titrated endogenous EF in an EwS cell line and linked phenotypic states to distinct EF thresholds. Strikingly, modest EF depletion promoted a pro-metastatic phenotype, which was diminished upon near-complete EF loss. Transcriptomic analysis revealed distinct gene clusters with heterogenous response patterns to varying EF dosage. Target genes most sensitive to subtle EF depletion contained GGAA microsatellites in EF-bound enhancers. Furthermore, we identified Krüppel-like zinc-finger transcription factors to be associated with EF-repressed EMP genes. EF rescue after partial depletion for a transient period identified persistently dysregulated genes associated with poor prognosis. This study underscores the therapeutic challenge of insufficient EF inhibition and provides a foundation for exploiting oncoprotein dynamics to uncover therapeutic vulnerabilities in fusion-driven cancers.
2025-04-10 | GSE291133 | GEO
Project description:The mechanisms underlying tumor cell plasticity driving drug resistance and disease progression remain poorly understood. In Ewing sarcoma (EwS), variations in EWS::FLI1 (EF) activity have been associated with epithelial-mesenchymal plasticity (EMP). Using degron technology, we titrated endogenous EF in an EwS cell line and linked phenotypic states to distinct EF thresholds. Strikingly, modest EF depletion promoted a pro-metastatic phenotype, which was diminished upon near-complete EF loss. Transcriptomic analysis revealed distinct gene clusters with heterogenous response patterns to varying EF dosage. Target genes most sensitive to subtle EF depletion contained GGAA microsatellites in EF-bound enhancers. Furthermore, we identified Krüppel-like zinc-finger transcription factors to be associated with EF-repressed EMP genes. EF rescue after partial depletion for a transient period identified persistently dysregulated genes associated with poor prognosis. This study underscores the therapeutic challenge of insufficient EF inhibition and provides a foundation for exploiting oncoprotein dynamics to uncover therapeutic vulnerabilities in fusion-driven cancers.
2025-04-10 | GSE291060 | GEO
Project description:A673 Ewing's sarcoma cells containing either control RNAi retroviral constructs (luc-RNAi), or RNAi retroviral constructs targeting the endogenous EWS/FLI fusion transcript (either EF-2-RNAi or EF-4-RNAi). Experiment Overall Design: Eight samples total. Four luc-RNAi, and four EWS/FLI knockdown constructs (two each of EF-2-RNAi or EF-4-RNAi).
2008-06-13 | E-GEOD-4560 | biostudies-arrayexpress
Project description:The contradiction between ‘high-yielding’ and ‘early-maturing’ hampers further improvement on annual rice yield. Here we reported the positional cloning of a major maturity duration-regulatory gene, Early flowering-completely dominant (Ef-cd), and demonstrated that natural variation in Ef-cd could be used to overcome the above contradictory. The Ef-cd locus gives rise to a long noncoding RNA (lncRNA) antisense transcript overlapping the OsSOC1 gene. Ef-cd lncRNA expression positively correlates with the expression of OsSOC1 and H3K36me3 deposition. Field test comparisons of early-maturing Ef-cd near-isogenic lines (NILs) with their wild types as well as the derivative early-maturing hybrids with their wild-type hybrids conducted under different latitudes determined that early-maturing Ef-cd allele shortens maturity duration (ranging from 7 to 20 days) without a concomitant yield penalty. Ef-cd facilitates nitrogen utilization and also improves the photosynthesis rate. Analysis of 1,439 elite hybrid rice varieties revealed that the 16 homozygotes and 299 heterozygotes possessing Ef-cd matured significantly earlier. Therefore, Ef-cd could be a vital contributor of elite early-maturing hybrid varieties in balancing grain yield with maturity duration.
2019-07-03 | GSE133746 | GEO
Project description:Bacillus anthracis, the causative agent of anthrax, secretes three toxin proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF). PA is a transporter of LF and EF into host cells by receptor-mediated endocytosis. LF is a metalloprotease that cleaves mitogen-activated protein kinase (MAPK) kinases (MKK), while EF is an adenylate cyclase, which converts ATP to cAMP. We used microarrays to decipher the specific gene regulation in edema toxin (ET), the complex of EF and PA, treated mouse bone marrow derived macrophages. Experiment Overall Design: BMDM were treated with 1 mg/ml of ET and the RNAs were purified at 0, 2, and 4h after toxin treatment.
2008-06-16 | E-GEOD-9184 | biostudies-arrayexpress
Project description:The pathogenesis of eosinophilic fasciitis (EF) and morphea is poorly understood. We analyzed skin biopsies from EF and morphea patients compared to adult healthy skin (HS) using gene expression profiling, Ingenuity Pathway Analysis, and immunostaining. EF gene expression showed significant overlap with morphea. 51/61 differentially expressed genes (DEG), 80/99 canonical pathways, and 40/51 upstream regulators were shared in EF and morphea. Both conditions exhibited robust T cell activation and cytotoxic signatures despite their pauci-inflammatory histological appearance, suggesting small numbers of T cells may drive injury, inflammation, and fibrosis. EF and morphea shared signatures of necroptosis, self-DNA recognition, cGAS/STING activation, induction of types I, II, and III interferon signaling, and fibrosis. Seven JAK/STAT molecules were significantly upregulated in EF and nine were upregulated in morphea. Compared to HS, TYK2 was the most significant JAK molecule upregulated in EF (p=0.0007) and morphea (p=0.0002). Immunostaining demonstrated activated interferon-related molecules JAK1 and STAT1 in T cells, dendritic cells, and macrophages in both diseases. This study identifies shared molecular mechanisms of EF and morphea and demonstrates strong pathophysiologic similarities between the two diseases. Our findings indicate that targeted inhibition of JAK/STAT molecules and mediators of necroptosis may be beneficial in treating these fibrotic diseases.
2025-05-19 | GSE278882 | GEO
Project description:Myocardial left ventricular biopsies from male patients (n=6) with isolated aortic stenosis and pronounced left ventricular hypertrophy undergoing aortic valve replacement were harvested either from hearts with normal ejection fraction (EF,>50%) or with low EF (<30%). Biopsies were further obtained from non-hypertrophied hearts with normal EF (>60%) from coronary artery disease patients undergoing coronary artery bypass graft surgery (n=3). Total RNA isolated from biopsies was analyzed using Affymetrix HG-U133A and U133B GeneChip sets.
2010-12-15 | E-MEXP-2296 | biostudies-arrayexpress
Project description:Bacillus anthracis, the causative agent of anthrax, secretes three toxin proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF). PA is a transporter of LF and EF into host cells by receptor-mediated endocytosis. LF is a metalloprotease that cleaves mitogen-activated protein kinase (MAPK) kinases (MKK), while EF is an adenylate cyclase, which converts ATP to cAMP. We used microarrays to decipher the specific gene regulation in edema toxin (ET), the complex of EF and PA, treated mouse bone marrow derived macrophages. Keywords: Time course
2007-09-28 | GSE9184 | GEO