ArticleMolecular cancer research : MCR2012
EWS/FLI1 regulates EYA3 in Ewing sarcoma via modulation of miRNA-708, resulting in increased cell survival and chemoresistance.
Article in Molecular cancer research : MCR, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Non-coding RNAs in drug and radiation resistance of bone and soft-tissue sarcoma: a systematic review.eLife · 2022Pooled it
- The Double Life of microRNAs in Bone Sarcomas: Oncogenic Drivers and Tumor Suppressors.International journal of molecular sciences · 2025Review
- EYA3 regulation of NF-κB and CCL2 suppresses cytotoxic NK cells in the premetastatic niche to promote TNBC metastasis.Science advances · 2025Article
- All eyes on Eya: A unique transcriptional co-activator and phosphatase in cancer.Biochimica et biophysica acta. Reviews on cancer · 2024Review
- In Vitro Phosphatase Assays for the Eya2 Tyrosine Phosphatase.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Review
- Targeted Therapy for EWS-FLI1 in Ewing Sarcoma.Cancers · 2023Review
- The value of EYA1/3/4 in clear cell renal cell carcinoma: a study from multiple databases.Scientific reports · 2023Article
- Review
- Inhibitors of EYA3 Protein in Ewing Sarcoma.Asian Pacific journal of cancer prevention : APJCP · 2022Article
- Review
- Epi-miRNAs: Regulators of the Histone Modification Machinery in Human Cancer.Journal of oncology · 2022Review
- Targeting EYA2 tyrosine phosphatase activity in glioblastoma stem cells induces mitotic catastrophe.The Journal of experimental medicine · 2021Article
- The Landscape of Regulatory Noncoding RNAs in Ewing's Sarcoma.Biomedicines · 2021Review
- Targeting EYA3 in Ewing Sarcoma Retards Tumor Growth and Angiogenesis.Molecular cancer therapeutics · 2021Article
- Challenges in modeling EWS-FLI1-driven transgenic mouse model for Ewing sarcoma.American journal of translational research · 2021Review
- The multi-functional eyes absent proteins.Critical reviews in biochemistry and molecular biology · 2020Review
- miR-708-5p targets oncogenic prostaglandin E2 production to suppress a pro-tumorigenic phenotype in lung cancer cells.Oncotarget · 2020Article
- Understanding the Mechanisms by Which Epigenetic Modifiers Avert Therapy Resistance in Cancer.Frontiers in oncology · 2020Review
- MicroRNA-708 Suppresses Cell Proliferation and Enhances Chemosensitivity of Cervical Cancer Cells to cDDP by Negatively Targeting Timeless.OncoTargets and therapy · 2020Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Ewing sarcoma is an aggressive pediatric cancer of the bone and soft tissue, in which patients whose tumors have a poor histologic response to initial chemotherapy have a poor overall prognosis. Therefore, it is important to identify molecules involved in resistance to chemotherapy. Herein, we show that the DNA repair protein and transcriptional cofactor, EYA3, is highly expressed in Ewing sarcoma tumor samples and cell lines compared with mesenchymal stem cells, the presumed cell-of-origin of Ewing sarcoma, and that it is regulated by the EWS/FLI1 fusion protein transcription factor. We further show that EWS/FLI1 mediates upregulation of EYA3 via repression of miR-708, a miRNA that targets the EYA3 3'-untranslated region, rather than by binding the EYA3 promoter directly. Importantly, we show that high levels of EYA3 significantly correlate with low levels of miR-708 in Ewing sarcoma samples, suggesting that this miR-mediated mechanism of EYA3 regulation holds true in human cancers. Because EYA proteins are important for cell survival during development, we examine, and show, that loss of EYA3 decreases survival of Ewing sarcoma cells. Most importantly, knockdown of EYA3 in Ewing sarcoma cells leads to sensitization to DNA-damaging chemotherapeutics used in the treatment of Ewing sarcoma, and as expected, after chemotherapeutic treatment, EYA3 knockdown cells repair DNA damage less effectively than their control counterparts. These studies identify EYA3 as a novel mediator of chemoresistance in Ewing sarcoma and define the molecular mechanisms of both EYA3 overexpression and of EYA3-mediated chemoresistance.
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Registered trials
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