2021
Reprogramming of bivalent chromatin states in NRAS mutant melanoma suggests PRC2 inhibition as a therapeutic strategy
Terranova C, Tang M, Maitituoheti M, Raman A, Ghosh A, Schulz J, Amin S, Orouji E, Tomczak K, Sarkar S, Oba J, Creasy C, Wu C, Khan S, Lazcano R, Wani K, Singh A, Barrodia P, Zhao D, Chen K, Haydu L, Wang W, Lazar A, Woodman S, Bernatchez C, Rai K. Reprogramming of bivalent chromatin states in NRAS mutant melanoma suggests PRC2 inhibition as a therapeutic strategy. Cell Reports 2021, 36: 109410. PMID: 34289358, PMCID: PMC8369408, DOI: 10.1016/j.celrep.2021.109410.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorCell ProliferationChromatinEnhancer of Zeste Homolog 2 ProteinFemaleGTP PhosphohydrolasesHistonesHumansMelanocytesMelanomaMembrane ProteinsMesodermMice, NudeMitogen-Activated Protein Kinase KinasesMutationNeoplasm MetastasisPolycomb Repressive Complex 2Transcription, GeneticTumor BurdenConceptsHistone H3 lysine 27 trimethylationH3 lysine 27 trimethylationBivalent chromatin stateCell identity genesLysine 27 trimethylationKey epigenetic alterationsNRAS mutantsMaster transcription factorBivalent domainsChromatin statePRC2 inhibitionEpigenetic elementsTranscription factorsEpigenetic alterationsGenetic driversMesenchymal phenotypeNRAS-mutant melanomaState profilingTherapeutic vulnerabilitiesInvasive capacityPharmacological inhibitionMutantsTherapeutic strategiesMelanoma samplesMutant melanoma patients
2020
KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer
Alam H, Tang M, Maitituoheti M, Dhar S, Kumar M, Han C, Ambati C, Amin S, Gu B, Chen T, Lin Y, Chen J, Muller F, Putluri N, Flores E, DeMayo F, Baseler L, Rai K, Lee M. KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer. Cancer Cell 2020, 37: 599-617.e7. PMID: 32243837, PMCID: PMC7178078, DOI: 10.1016/j.ccell.2020.03.005.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma of LungAnimalsAntimetabolitesApoptosisBiomarkers, TumorCell ProliferationDeoxyglucoseDNA-Binding ProteinsEnhancer Elements, GeneticGene Expression Regulation, NeoplasticGlycolysisHistone-Lysine N-MethyltransferaseHistonesHumansLung NeoplasmsMiceMice, KnockoutMice, NudeMutationMyeloid-Lymphoid Leukemia ProteinNeoplasm ProteinsPeriod Circadian ProteinsPrognosisTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsLung cancerLung-specific lossHuman lung cancer cellsExpression of Per2Lung cancer cellsHistone methyltransferase KMT2DLung tumor suppressorTumor suppressive roleMultiple glycolytic genesLung tumorigenesisEpigenetic modifiersPharmacological inhibitionTherapeutic vulnerabilitiesGlycolytic inhibitorCancerCancer cellsKMT2DFunction mutationsTumor suppressorPer2GlycolysisGlycolytic genesMutationsMice
2017
Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression
Fiziev P, Akdemir K, Miller J, Keung E, Samant N, Sharma S, Natale C, Terranova C, Maitituoheti M, Amin S, Martinez-Ledesma E, Dhamdhere M, Axelrad J, Shah A, Cheng C, Mahadeshwar H, Seth S, Barton M, Protopopov A, Tsai K, Davies M, Garcia B, Amit I, Chin L, Ernst J, Rai K. Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression. Cell Reports 2017, 19: 875-889. PMID: 28445736, PMCID: PMC5473172, DOI: 10.1016/j.celrep.2017.03.078.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationCell LineCell ProliferationChromatinChromatin ImmunoprecipitationDisease-Free SurvivalEpigenomicsHistone Deacetylase InhibitorsHistone DeacetylasesHistonesHumansHydroxamic AcidsKaplan-Meier EstimateMelanomaPrincipal Component AnalysisPTEN PhosphohydrolaseRNA InterferenceRNA, Small InterferingSignal TransductionVorinostatConceptsChromatin state transitionsMelanoma progressionChromatin state changesGene expression patternsCancer regulatory genesChromatin stateEpigenomic profilingEpigenomic changesEpigenomic analysisTumorigenic stateEpigenetic modificationsTranscriptomic analysisRegulatory regionsHistone acetylationAcetylation changesHistone deacetylase inhibitorsExpression patternsHyperproliferative phenotypeAcetylation levelsTumorigenic cellsHuman melanoma cellsFunctional rolePhenotypic modelDeacetylase inhibitorsMelanoma cells
2016
miR-182-5p Induced by STAT3 Activation Promotes Glioma Tumorigenesis
Xue J, Zhou A, Wu Y, Morris S, Lin K, Amin S, Verhaak R, Fuller G, Xie K, Heimberger A, Huang S. miR-182-5p Induced by STAT3 Activation Promotes Glioma Tumorigenesis. Cancer Research 2016, 76: 4293-4304. PMID: 27246830, PMCID: PMC5033679, DOI: 10.1158/0008-5472.can-15-3073.Peer-Reviewed Original ResearchConceptsProtocadherin-8Glioma tumorigenesisProtein-coding genesMiRNA gene transcriptionCandidate target genesExpression of STAT3Gene transcriptionBioinformatics analysisTarget genesSTAT3/miRSTAT3 knockdownPCDH8 expressionSTAT3 inhibitorAberrant activationGlioblastoma tissuesSTAT3Expression levelsInvasive capacityTranscriptionTumorigenesisGlioma progressionGenesCritical roleKnockdownP-STAT3
2011
Significant Biological Role of Sp1 Transactivation in Multiple Myeloma
Fulciniti M, Amin S, Nanjappa P, Rodig S, Prabhala R, Li C, Minvielle S, Tai Y, Tassone P, Avet-Loiseau H, Hideshima T, Anderson K, Munshi N. Significant Biological Role of Sp1 Transactivation in Multiple Myeloma. Clinical Cancer Research 2011, 17: 6500-6509. PMID: 21856768, PMCID: PMC4318245, DOI: 10.1158/1078-0432.ccr-11-1036.Peer-Reviewed Original ResearchConceptsBone marrow stromal cellsSp1 activitySp1 knockdownTranscription factor specificity protein 1Caspase-9-dependent apoptosisCritical cell cycleSp1 DNA bindingSp1-responsive promotersSpecificity protein 1Cell growthFirefly luciferase reporter geneImportant transcription factorImportant regulatory roleLuciferase reporter geneSignificant biological roleApoptosis-related genesSp1 transactivationShort hairpin RNASp1 DNACellular processesTranscription factorsPromoter elementsMarrow stromal cellsReporter geneMM cells
2010
Elevated IL-17 produced by T h 17 cells promotes myeloma cell growth and inhibits immune function in multiple myeloma
Prabhala R, Pelluru D, Fulciniti M, Prabhala H, Nanjappa P, Song W, Pai C, Amin S, Tai Y, Richardson P, Ghobrial I, Treon S, Daley J, Anderson K, Kutok J, Munshi N. Elevated IL-17 produced by T h 17 cells promotes myeloma cell growth and inhibits immune function in multiple myeloma. Blood 2010, 115: 5385-5392. PMID: 20395418, PMCID: PMC2902136, DOI: 10.1182/blood-2009-10-246660.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsHealthy donor peripheral blood mononuclear cellsDonor peripheral blood mononuclear cellsIL-17Multiple myelomaBM mononuclear cellsMyeloma cell growthBone marrowBone marrow stromal cellsIL-22Mononuclear cellsHealthy donorsImmune functionT helper 17 (Th17) cellsElevated IL-17Observed immune dysfunctionSerum IL-17IL-23 productionBlood mononuclear cellsAnti-MM activityIL-17 receptorHuman multiple myelomaMurine xenograft modelImportant therapeutic targetMM pathobiology