0000000000053986

AUTHOR

Jun Qi

showing 4 related works from this author

CRISPR-Cas9 screen reveals a MYCN-amplified neuroblastoma dependency on EZH2.

2018

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…

0301 basic medicineCellular differentiationMedical and Health SciencesNeuroblastomaSUZ12Oncogene MYCNCRISPR-Cas SystemCancerPediatricNeuronsN-Myc Proto-Oncogene ProteinTumorEZH2EpigeneticCell DifferentiationGeneral MedicineUp-RegulationGene Expression Regulation NeoplasticOncology5.1 PharmaceuticalsEpigeneticsDevelopment of treatments and therapeutic interventionsHumanResearch ArticlePediatric Research InitiativePediatric CancerImmunologymacromolecular substancesBiologyN-Myc Proto-Oncogene ProteinCell Line03 medical and health sciencesRare DiseasesNeuroblastomaCell Line TumormedicineGeneticsHumansEnhancer of Zeste Homolog 2 ProteinTranscription factorneoplasmsNeoplasticHuman GenomeNeurosciencesGene AmplificationNeuronmedicine.disease030104 developmental biologyGene Expression RegulationCancer researchHistone deacetylaseCRISPR-Cas SystemsThe Journal of clinical investigation
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Abstract 1126: Efficacy of BET bromodomain inhibition in Kras-positive non-small cell lung cancer.

2013

Abstract Amplification of MYC is one of the most common genetic alterations in lung cancer, contributing to a myriad of phenotypes associated with growth, invasion and drug resistance. Murine genetics has established both the centrality of somatic alterations of Kras in lung cancer, as well as dependency of Kras-dependent tumors on c-Myc function. Unfortunately, drug-like small-molecule inhibitors of KRAS and c-Myc have yet to be realized. The recent discovery in hematologic malignancies that bromodomain inhibition impairs MYC expression and MYC-dependent transcriptional function prompted the possibility of targeting KRAS-driven NSCLC with a potent, prototypical BET bromodomain inhibitor, J…

Genetically modified mouseCancer Researcheducation.field_of_studybusiness.industryMutantPopulationCancermedicine.diseasemedicine.disease_causerespiratory tract diseasesBromodomainOncologyDownregulation and upregulationImmunologymedicineCancer researchKRASLung cancereducationbusinessneoplasmsCancer Research
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Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer.

2016

Abstract As a master regulator of chromatin function, the lysine methyltransferase EZH2 orchestrates transcriptional silencing of developmental gene networks. Overexpression of EZH2 is commonly observed in human epithelial cancers, such as non–small cell lung carcinoma (NSCLC), yet definitive demonstration of malignant transformation by deregulated EZH2 remains elusive. Here, we demonstrate the causal role of EZH2 overexpression in NSCLC with new genetically engineered mouse models of lung adenocarcinoma. Deregulated EZH2 silences normal developmental pathways, leading to epigenetic transformation independent of canonical growth factor pathway activation. As such, tumors feature a transcrip…

0301 basic medicineModels MolecularLung Neoplasmsmedicine.medical_treatmentMolecular ConformationGene ExpressionAntineoplastic Agentsmacromolecular substancesBiologymedicine.disease_causeArticleMalignant transformationTargeted therapy03 medical and health sciencesMiceStructure-Activity RelationshipCell Line TumormedicineAnimalsHumansEnhancer of Zeste Homolog 2 ProteinMolecular Targeted TherapyLung cancerPromoter Regions GeneticGene Expression ProfilingEZH2Cancermedicine.diseaseMagnetic Resonance ImagingXenograft Model Antitumor AssaysChromatinrespiratory tract diseasesGene Expression Regulation NeoplasticDisease Models Animal030104 developmental biologyCell Transformation NeoplasticEnhancer Elements GeneticOncologyDrug DesignCancer researchAdenocarcinomaKRASEpigenetic therapyCancer discovery
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Efficacy of BET Bromodomain Inhibition in Kras-Mutant Non–Small Cell Lung Cancer

2013

Abstract Purpose: Amplification of MYC is one of the most common genetic alterations in lung cancer, contributing to a myriad of phenotypes associated with growth, invasion, and drug resistance. Murine genetics has established both the centrality of somatic alterations of Kras in lung cancer, as well as the dependency of mutant Kras tumors on MYC function. Unfortunately, drug-like small-molecule inhibitors of KRAS and MYC have yet to be realized. The recent discovery, in hematologic malignancies, that bromodomain and extra-terminal (BET) bromodomain inhibition impairs MYC expression and MYC transcriptional function established the rationale of targeting KRAS-driven non–small cell lung cance…

Cancer ResearchLKB1Lung NeoplasmsMutantApoptosisMYCAMP-Activated Protein KinasesProtein Serine-Threonine KinasesBiologyNSCLCmedicine.disease_causeArticleProto-Oncogene Proteins c-mycProto-Oncogene Proteins p21(ras)MiceRNA interferenceCarcinoma Non-Small-Cell LungCell Line TumorKRASmedicineAnimalsRNA Small InterferingLung cancerneoplasmsCell ProliferationMice KnockoutGene knockdownCell growthNuclear ProteinsCancerAzepinesTriazolesBETmedicine.diseaseMolecular biologydigestive system diseasesrespiratory tract diseasesBromodomainOncologyCancer researchRNA InterferenceKRASSignal TransductionTranscription FactorsClinical Cancer Research
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