ArticleLaboratory investigation; a journal of technical methods and pathology2015
Characterization and pharmacologic targeting of EZH2, a fetal retinal protein and epigenetic regulator, in human retinoblastoma.
Article in Laboratory investigation; a journal of technical methods and pathology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Tumor heterogeneity in retinoblastoma: a literature review.Cancer metastasis reviews · 2025Review
- The functional role of circular RNAs in the pathogenesis of retinoblastoma: a new potential biomarker and therapeutic target?Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- Integrative Multi-Omics Analysis of Oncogenic EZH2 Mutants: From Epigenetic Reprogramming to Molecular Signatures.International journal of molecular sciences · 2023Article
- Novel insights into histone lysine methyltransferases in cancer therapy: From epigenetic regulation to selective drugs.Journal of pharmaceutical analysis · 2023Review
- Interruption of aberrant chromatin looping is required for regenerating RB1 function and suppressing tumorigenesis.Communications biology · 2022Article
- Active RB causes visible changes in nuclear organization.The Journal of cell biology · 2022Article
- Role of non-coding RNAs and exosomal non-coding RNAs in retinoblastoma progression.Frontiers in cell and developmental biology · 2022Review
- Chromatin regulators in retinoblastoma: Biological roles and therapeutic applications.Journal of cellular physiology · 2021Review
- Ubiquitous Chromatin Modifiers in Congenital Retinal Diseases: Implications for Disease Modeling and Regenerative Medicine.Trends in molecular medicine · 2021Review
- p53 Integrates Temporal WDR5 Inputs during Neuroectoderm and Mesoderm Differentiation of Mouse Embryonic Stem Cells.Cell reports · 2020Article
- Diosgenin and GSK126 Produce Synergistic Effects on Epithelial-Mesenchymal Transition in Gastric Cancer Cells by Mediating EZH2 via the Rho/ROCK Signaling Pathway.OncoTargets and therapy · 2020Article
- Review
- Non-Coding RNAs in Retinoblastoma.Frontiers in genetics · 2019Review
- MicroRNA-101-3p inhibits proliferation in retinoblastoma cells by targeting EZH2 and HDAC9.Experimental and therapeutic medicine · 2018Article
- Inhibition of EZH2 and EGFR produces a synergistic effect on cell apoptosis by increasing autophagy in gastric cancer cells.OncoTargets and therapy · 2018Article
- Epigenetic regulation of human retinoblastoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- The Targetable Epigenetic Tumor Protein EZH2 is Enriched in Intraocular Medulloepithelioma.Investigative ophthalmology & visual science · 2016Article
- Postnatal onset of retinal degeneration by loss of embryonic Ezh2 repression of Six1.Scientific reports · 2016Article
- Polycomb and Trithorax Group Proteins: The Long Road from Mutations in Drosophila to Use in Medicine.Acta naturaeArticle
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
Retinoblastoma (RB) is the most common primary intraocular cancer in children, and the third most common cancer overall in infants. No molecular-targeted therapy for this lethal tumor exists. Since the tumor suppressor RB1, whose genetic inactivation underlies RB, is upstream of the epigenetic regulator EZH2, a pharmacologic target for many solid tumors, we reasoned that EZH2 might regulate human RB tumorigenesis. Histologic and immunohistochemical analyses were performed using an EZH2 antibody in sections from 43 samples of primary, formalin-fixed, paraffin-embedded human RB tissue, cryopreserved mouse retina, and in whole cell lysates from human RB cell lines (Y79 and WERI-Rb1), primary human fetal retinal pigment epithelium (RPE) and fetal and adult retina, mouse retina and embryonic stem (ES) cells. Although enriched during fetal human retinal development, EZH2 protein was not present in the normal postnatal retina. However, EZH2 was detected in all 43 analyzed human RB specimens, indicating that EZH2 is a fetal protein expressed in postnatal human RB. EZH2 expression marked single RB cell invasion into the optic nerve, a site of invasion whose involvement may influence the decision for systemic chemotherapy. To assess the role of EZH2 in RB cell survival, human RB and primary RPE cells were treated with two EZH2 inhibitors (EZH2i), GSK126 and SAH-EZH2 (SAH). EZH2i impaired intracellular adenosine triphosphate (ATP) production, an indicator of cell viability, in a time and dose-dependent manner, but did not affect primary human fetal RPE. Thus, aberrant expression of a histone methyltransferase protein is a feature of human RB. This is the first time this mechanism has been implicated for an eye, adnexal, or orbital tumor. The specificity of EZH2i toward human RB cells, but not RPE, warrants further in vivo testing in animal models of RB, especially those EZH2i currently in clinical trials for solid tumors and lymphoma.
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