ArticleEpigenetics2014
Overexpression of HOX genes is prevalent in Ewing sarcoma and is associated with altered epigenetic regulation of developmental transcription programs.
Article in Epigenetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 68 citations in OpenAlex.
- A Practical Compass to Biological Digital Resources and Omics Integration in Ewing Sarcoma.Methods in molecular biology (Clifton, N.J.) · 2027Article
- KDM6 Demethylases Contribute to EWSR1::FLI1-Driven Oncogenic Reprogramming in Ewing Sarcoma.Cancer research · 2025Article
- FET fusion oncoproteins enrich SWI/SNF complex subtypes and interaction partners.Cellular & molecular biology letters · 2025Article
- Druggable upregulated proteins in EWS-FLI-driven Ewing sarcoma as emerging new therapeutic targets.American journal of translational research · 2025Review
- Menin in Cancer.Genes · 2024Review
- Uterine Tumor Resembling Ovarian Sex-Cord Tumor (UTROSCT): A Rare Polyphenotypic Neoplasm.Diagnostics (Basel, Switzerland) · 2024Review
- Maintenance of neuronal identity in C. elegans and beyond: Lessons from transcription and chromatin factors.Seminars in cell & developmental biology · 2024Review
- EWS/FLI1 Characterization, Activation, Repression, Target Genes and Therapeutic Opportunities in Ewing Sarcoma.International journal of molecular sciences · 2023Review
- Integrative analyses of bulk microarray data to discover genes, pathways, and immune infiltration characteristics associated with targeting of Ewing sarcoma.Journal of cancer research and clinical oncology · 2023Article
- Fli1 and Tissue Fibrosis in Various Diseases.International journal of molecular sciences · 2023Review
- Identification and validation of a novel ubiquitination-related geneFrontiers in oncology · 2023Article
- Bmi-1: A master regulator of head and neck cancer stemness.Frontiers in oral health · 2023Review
- Systematic multi-omics cell line profiling uncovers principles of Ewing sarcoma fusion oncogene-mediated gene regulation.Cell reports · 2022Article
- EWS::FLI1 and HOXD13 Control Tumor Cell Plasticity in Ewing Sarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Recurrent chromosomal translocations in sarcomas create a megacomplex that mislocalizes NuA4/TIP60 to Polycomb target loci.Genes & development · 2022Article
- Inhibitor of DNA binding 2 (ID2) regulates the expression of developmental genes and tumorigenesis in ewing sarcoma.Oncogene · 2022Article
- The importance of fusion protein activity in Ewing sarcoma and the cell intrinsic and extrinsic factors that regulate it: A review.Frontiers in oncology · 2022Review
- Screening of Potential Key Biomarkers for Ewing Sarcoma: Evidence from Gene Array Analysis.International journal of general medicine · 2022Article
- One oncogene, several vulnerabilities: EWS/FLI targeted therapies for Ewing sarcoma.Journal of bone oncology · 2021Article
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Authors and funding
10 authors at 6 institutions in 5 countries.
Funding
Abstract
The polycomb proteins BMI-1 and EZH2 are highly overexpressed by Ewing sarcoma (ES), a tumor of stem cell origin that is driven by EWS-ETS fusion oncogenes, most commonly EWS-FLI1. In the current study we analyzed expression of transcription programs that are controlled by polycomb proteins during embryonic development to determine if they are abnormal in ES. Our results show that polycomb target gene expression in ES deviates from normal tissues and stem cells and that, as expected, most targets are relatively repressed. However, we also discovered a paradoxical up regulation of numerous polycomb targets and these were highly enriched for homeobox (HOX) genes. Comparison of HOX profiles between malignant and non-malignant tissues revealed a distinctive HOX profile in ES, which was characterized by overexpression of posterior HOXD genes. In addition, ectopic expression of EWS-FLI1 during stem cell differentiation led to aberrant up regulation of posterior HOXD genes. Mechanistically, this up regulation was associated with altered epigenetic regulation. Specifically, ES and EWS-FLI1+ stem cells displayed a relative loss of polycomb-dependent H3K27me3 and gain of trithorax-dependent H3K4me3 at the promoters of posterior HOXD genes and also at the HOXD11.12 polycomb response element. In addition, a striking correlation was evident between HOXD13 and other genes whose regulation is coordinately regulated during embryonic development by distal enhancer elements. Together, these studies demonstrate that epigenetic regulation of polycomb target genes, in particular HOXD genes, is altered in ES and that these changes are mediated downstream of EWS-FLI1.
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