ArticleThe Journal of clinical investigation2018
CRISPR-Cas9 screen reveals a MYCN-amplified neuroblastoma dependency on EZH2.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
What it found
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Who cites it
112 citing papers in PubMed, 156 citations in OpenAlex.
- Precision gene editing in infant neuroblastoma: a review of nanoparticle: enabled CRISPR/Cas9 therapies.Molecular biology reports · 2026Review
- High-resolution CRISPR/Cas9 screens identify PAK2 as a suppressor of macrophage proliferation.bioRxiv : the preprint server for biology · 2026Article
- Targeting MYC-Driven Cancers: From Oncogenic Addiction to Therapeutic Vulnerability.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- 5-hydroxymethylcytosine deposition mediates Polycomb repressive complex 2 function iniScience · 2026Article
- Single-cell and spatial omics reveals region-specific plasticity and therapeutic vulnerabilities in metastatic high-risk neuroblastoma.Science advances · 2026Article
- Inhibition of USP7 Destabilizes the Noncanonical PRC1.1 Complex and Induces Neuroblastoma Differentiation.Molecular cancer research : MCR · 2026Article
- Review
- Prime Editing, CRISPR-Cas9, and NanoCas Genome Editing for Cancer Treatment.Molecular biotechnology · 2026Review
- Cancer neuroscience: signaling pathways and new therapeutic strategies for cancer.Signal transduction and targeted therapy · 2026Review
- CDK2 inhibition promotes neuronal differentiation in neuroblastoma.Scientific reports · 2026Article
- Article
- Molecular alterations in high-grade neuroendocrine tumors of the small intestine.The Journal of pathology · 2026Article
- Developmentally relevant proteins contribute to chemotherapeutic resistance in neuroblastoma.Frontiers in oncology · 2026Review
- A Functional Shift of IGFBP3 in Osteoarthritis: From Cartilage Protection to Disease Promotion.Journal of inflammation research · 2026Review
- SGSS05-NS3, a covalent SETD8 inhibitor that activates p53 pathway in neuroblastoma.Journal of experimental & clinical cancer research : CR · 2025Article
- KDM6 Demethylases Contribute to EWSR1::FLI1-Driven Oncogenic Reprogramming in Ewing Sarcoma.Cancer research · 2025Article
- Synthetic lethality of EZH2 and DNMT Inhibition suppresses neuroblastoma proliferation via MYCN destabilization.BMC cancer · 2025Article
- Advances in RNA-based cancer therapeutics: pre-clinical and clinical implications.Molecular cancer · 2025Review
- Review
- Review
52 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
33 authors at 7 institutions in 1 country.
Funding
Abstract
Pharmacologically difficult targets, such as MYC transcription factors, represent a major challenge in cancer therapy. For the childhood cancer neuroblastoma, amplification of the oncogene MYCN is associated with high-risk disease and poor prognosis. Here, we deployed genome-scale CRISPR-Cas9 screening of MYCN-amplified neuroblastoma and found a preferential dependency on genes encoding the polycomb repressive complex 2 (PRC2) components EZH2, EED, and SUZ12. Genetic and pharmacological suppression of EZH2 inhibited neuroblastoma growth in vitro and in vivo. Moreover, compared with neuroblastomas without MYCN amplification, MYCN-amplified neuroblastomas expressed higher levels of EZH2. ChIP analysis showed that MYCN binds at the EZH2 promoter, thereby directly driving expression. Transcriptomic and epigenetic analysis, as well as genetic rescue experiments, revealed that EZH2 represses neuronal differentiation in neuroblastoma in a PRC2-dependent manner. Moreover, MYCN-amplified and high-risk primary tumors from patients with neuroblastoma exhibited strong repression of EZH2-regulated genes. Additionally, overexpression of IGFBP3, a direct EZH2 target, suppressed neuroblastoma growth in vitro and in vivo. We further observed strong synergy between histone deacetylase inhibitors and EZH2 inhibitors. Together, these observations demonstrate that MYCN upregulates EZH2, leading to inactivation of a tumor suppressor program in neuroblastoma, and support testing EZH2 inhibitors in patients with MYCN-amplified neuroblastoma.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.