Featured Publications
Single-cell microRNA-mRNA co-sequencing reveals non-genetic heterogeneity and mechanisms of microRNA regulation
Wang N, Zheng J, Chen Z, Liu Y, Dura B, Kwak M, Xavier-Ferrucio J, Lu YC, Zhang M, Roden C, Cheng J, Krause DS, Ding Y, Fan R, Lu J. Single-cell microRNA-mRNA co-sequencing reveals non-genetic heterogeneity and mechanisms of microRNA regulation. Nature Communications 2019, 10: 95. PMID: 30626865, PMCID: PMC6327095, DOI: 10.1038/s41467-018-07981-6.Peer-Reviewed Original ResearchConceptsSame single cellMicroRNA-mRNASingle cellsGenome-scale analysisNon-genetic cellNon-genetic heterogeneityMultiple omic profilesGenomic approachesMicroRNA regulationMolecular regulationTarget mRNAsExpression variabilityCellular pathwaysRegulatory relationshipsLevels of microRNAsIntercellular heterogeneityOmics profilesIntercellular variabilityCell heterogeneityMRNA profilesMicroRNAsMRNACellsRegulationExpressionNovel determinants of mammalian primary microRNA processing revealed by systematic evaluation of hairpin-containing transcripts and human genetic variation
Roden C, Gaillard J, Kanoria S, Rennie W, Barish S, Cheng J, Pan W, Liu J, Cotsapas C, Ding Y, Lu J. Novel determinants of mammalian primary microRNA processing revealed by systematic evaluation of hairpin-containing transcripts and human genetic variation. Genome Research 2017, 27: 374-384. PMID: 28087842, PMCID: PMC5340965, DOI: 10.1101/gr.208900.116.Peer-Reviewed Original ResearchConceptsPri-miRNA processingHuman genetic variationGenetic variationPrimary sequence motifsPrimary microRNA processingMiRNA biogenesisDisease-causing mutationsPri-miRNAsPrimary miRNAsSequence motifsMiRNA hairpinsMicroRNA processingMature microRNAsSequence featuresRNA hairpinsComputational pipelineNovel determinantStem lengthUnpaired basesHairpinTranscriptsStemBiogenesisGenomeMiRNAsA Molecular Chipper technology for CRISPR sgRNA library generation and functional mapping of noncoding regions
Cheng J, Roden CA, Pan W, Zhu S, Baccei A, Pan X, Jiang T, Kluger Y, Weissman SM, Guo S, Flavell RA, Ding Y, Lu J. A Molecular Chipper technology for CRISPR sgRNA library generation and functional mapping of noncoding regions. Nature Communications 2016, 7: 11178. PMID: 27025950, PMCID: PMC4820989, DOI: 10.1038/ncomms11178.Peer-Reviewed Original ResearchAnimalsBacterial ProteinsCell LineChromosome MappingCloning, MolecularClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated Protein 9DNADNA Restriction EnzymesEndonucleasesGene LibraryGenomeHumansMiceMicroRNAsOligonucleotide Array Sequence AnalysisRNA, Guide, CRISPR-Cas SystemsUntranslated RegionsmiR-125b promotes MLL-AF9–driven murine acute myeloid leukemia involving a VEGFA-mediated non–cell-intrinsic mechanism
Liu J, Guo B, Chen Z, Wang N, Iacovino M, Cheng J, Roden C, Pan W, Khan S, Chen S, Kyba M, Fan R, Guo S, Lu J. miR-125b promotes MLL-AF9–driven murine acute myeloid leukemia involving a VEGFA-mediated non–cell-intrinsic mechanism. Blood 2017, 129: 1491-1502. PMID: 28053194, PMCID: PMC5356452, DOI: 10.1182/blood-2016-06-721027.Peer-Reviewed Original Research
2020
The mir181ab1 cluster promotes kras-driven oncogenesis and progression in lung and pancreas
Valencia K, Erice O, Kostyrko K, Hausmann S, Guruceaga E, Tathireddy A, Flores NM, Sayles LC, Lee AG, Fragoso R, Sun TQ, Vallejo A, Roman M, Entrialgo-Cadierno R, Migueliz I, Razquin N, Fortes P, Lecanda F, Lu J, Ponz-Sarvise M, Chen CZ, Mazur PK, Sweet-Cordero EA, Vicent S. The mir181ab1 cluster promotes kras-driven oncogenesis and progression in lung and pancreas. Journal Of Clinical Investigation 2020, 130: 1879-1895. PMID: 31874105, PMCID: PMC7108928, DOI: 10.1172/jci129012.Peer-Reviewed Original ResearchConceptsPotential therapeutic targetNew molecular targetsPancreatic cancerMouse modelTherapeutic targetHuman cancer cellsDownstream effector pathwaysKRASMolecular targetsCancerCancer cellsEffector pathwaysKey modulatorNonredundant roleLungProliferative advantageProgressionUnknown roleOncogenesisPhenotypePatientsTherapyPancreasMicroRNA cluster
2019
Sfold Tools for MicroRNA Target Prediction
Rennie W, Kanoria S, Liu C, Carmack CS, Lu J, Ding Y. Sfold Tools for MicroRNA Target Prediction. Methods In Molecular Biology 2019, 1970: 31-42. PMID: 30963486, DOI: 10.1007/978-1-4939-9207-2_3.Peer-Reviewed Original Research
2018
ZEB1, ZEB2, and the miR-200 family form a counterregulatory network to regulate CD8+ T cell fates
Guan T, Dominguez CX, Amezquita RA, Laidlaw BJ, Cheng J, Henao-Mejia J, Williams A, Flavell RA, Lu J, Kaech SM. ZEB1, ZEB2, and the miR-200 family form a counterregulatory network to regulate CD8+ T cell fates. Journal Of Experimental Medicine 2018, 215: 1153-1168. PMID: 29449309, PMCID: PMC5881466, DOI: 10.1084/jem.20171352.Peer-Reviewed Original ResearchConceptsT cellsMemory CD8T cell fateMemory T cell survivalLong-term immunityT cell formationT cell survivalMiR-200 family membersGrowth factor βFamily membersTranscription factor ZEB1Effector CD8MiR-200 familyCD8Mesenchymal transitionReciprocal expression patternCell fateZEB1ZEB2Factor βCell survivalTGFCell formationUnknown genetic pathwaysCell fate decisions
2017
Capture, amplification, and global profiling of microRNAs from low quantities of whole cell lysate
Wang N, Cheng J, Fan R, Lu J. Capture, amplification, and global profiling of microRNAs from low quantities of whole cell lysate. Analyst 2017, 142: 3203-3211. PMID: 28765841, PMCID: PMC5605290, DOI: 10.1039/c7an00670e.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsGene Expression ProfilingGene Knockout TechniquesGene LibraryMiceMicroRNAsNIH 3T3 CellsConceptsWhole cell lysatesSmall non-coding RNAsComplex regulatory networkMiRNA profilingCell lysatesPost-transcriptional levelIsogenic cell linesNon-coding RNAsAdaptor ligationLow quantity samplesGenome scaleRegulatory networksGlobal profilingMiRNA captureGene expressionExpression profilesHuman diseasesMiRNA expressionLibrary preparationMiRNA alterationsCell typesMiRNA releaseRNA purificationMulti-step purificationCell linesThe microRNA miR-31 inhibits CD8+ T cell function in chronic viral infection
Moffett HF, Cartwright ANR, Kim HJ, Godec J, Pyrdol J, Äijö T, Martinez GJ, Rao A, Lu J, Golub TR, Cantor H, Sharpe AH, Novina CD, Wucherpfennig KW. The microRNA miR-31 inhibits CD8+ T cell function in chronic viral infection. Nature Immunology 2017, 18: 791-799. PMID: 28530712, PMCID: PMC5753758, DOI: 10.1038/ni.3755.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, ViralArenaviridae InfectionsCalciumCD8-Positive T-LymphocytesChromatin ImmunoprecipitationCytokinesDendritic CellsEnzyme-Linked Immunosorbent AssayFlow CytometryGene Expression ProfilingImmunoblottingInterferon Type ILymphocytic choriomeningitis virusMiceMice, KnockoutMicroRNAsNFATC Transcription FactorsReal-Time Polymerase Chain ReactionReceptors, Antigen, T-Cell
2016
STarMir Tools for Prediction of microRNA Binding Sites
Kanoria S, Rennie W, Liu C, Carmack CS, Lu J, Ding Y. STarMir Tools for Prediction of microRNA Binding Sites. Methods In Molecular Biology 2016, 1490: 73-82. PMID: 27665594, PMCID: PMC5353976, DOI: 10.1007/978-1-4939-6433-8_6.Peer-Reviewed Original ResearchConceptsMessenger RNAEndogenous short noncoding RNAsGene expressionMammalian biological processesHigh-throughput miRNATarget messenger RNAsShort noncoding RNAsMicroRNA Binding SitesCertain human diseasesCross-species validationTranslational repressionMiRNA functionGene regulationSeedless sitesMRNA degradationNoncoding RNAsRegulatory moleculesBiological processesSequence featuresHuman diseasesImmunoprecipitation studiesMiRNAComputational predictionsBinding sitesMiRNAsIn vivo mutagenesis of miRNA gene families using a scalable multiplexed CRISPR/Cas9 nuclease system
Narayanan A, Hill-Teran G, Moro A, Ristori E, Kasper DM, A. Roden C, Lu J, Nicoli S. In vivo mutagenesis of miRNA gene families using a scalable multiplexed CRISPR/Cas9 nuclease system. Scientific Reports 2016, 6: 32386. PMID: 27572667, PMCID: PMC5004112, DOI: 10.1038/srep32386.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChromosomesCRISPR-Cas SystemsGenomeMicroRNAsMultigene FamilyMutagenesisMutationZebrafishConceptsMiRNA familiesSingle guide RNAsMiRNA gene familiesHigher multicellular organismsMultiplexed CRISPR/Entire miRNA familiesMulticellular organismsMiRNA genesGene familySame physiological functionChromosomal locationPhylogenetic ancestorsGenomic sequencesCas9 nucleaseGuide RNACRISPR/Mutagenesis strategyNuclease systemPrimary sequenceVivo mutagenesisPhysiological functionsSecondary structureModel systemMiRNAsMutationsAdenosine-to-inosine RNA editing by ADAR1 is essential for normal murine erythropoiesis
Liddicoat BJ, Hartner JC, Piskol R, Ramaswami G, Chalk AM, Kingsley PD, Sankaran VG, Wall M, Purton LE, Seeburg PH, Palis J, Orkin SH, Lu J, Li JB, Walkley CR. Adenosine-to-inosine RNA editing by ADAR1 is essential for normal murine erythropoiesis. Experimental Hematology 2016, 44: 947-963. PMID: 27373493, PMCID: PMC5035604, DOI: 10.1016/j.exphem.2016.06.250.Peer-Reviewed Original ResearchMeSH KeywordsAdenosineAdenosine DeaminaseAnimalsCluster AnalysisErythrocyte IndicesErythroid CellsErythropoiesisGene ExpressionGene Expression ProfilingGene Expression Regulation, DevelopmentalGene Knockout TechniquesGranulocytesHematopoietic Stem Cell TransplantationInosineInterferonsMiceMicroRNAsMyelopoiesisOrgan SpecificityPhenotypeReceptors, InterferonRetroelementsRNA EditingRNA-Binding ProteinsSignal TransductionTranscription, GeneticConceptsRNA editingErythroid cellsNormal erythropoiesisHematopoietic stem/progenitorsHematopoietic cell typesInnate immune signalingStem/progenitorsEditing eventsErythroid-specific transcriptsEssential functionsImmune signalingMurine erythropoiesisADAR1Cell deathCell typesMyeloid-restricted deletionEditingRNAMicroRNA levelsErythropoiesisCellsProfound activationTranscriptsSignalingAdenosineRegulation of the DNA Methylation Landscape in Human Somatic Cell Reprogramming by the miR-29 Family
Hysolli E, Tanaka Y, Su J, Kim KY, Zhong T, Janknecht R, Zhou XL, Geng L, Qiu C, Pan X, Jung YW, Cheng J, Lu J, Zhong M, Weissman SM, Park IH. Regulation of the DNA Methylation Landscape in Human Somatic Cell Reprogramming by the miR-29 Family. Stem Cell Reports 2016, 7: 43-54. PMID: 27373925, PMCID: PMC4945581, DOI: 10.1016/j.stemcr.2016.05.014.Peer-Reviewed Original ResearchConceptsDNA methylation stateEmbryonic stem cellsInduced pluripotent stem cellsHuman somatic cell reprogrammingSomatic cell reprogrammingMethylation stateCell reprogrammingMiR-29 familyDNA methylation landscapeImportant epigenetic regulatorsStem cellsOverexpression of Oct4Global DNA methylationMiRNA-based approachesPluripotent stem cellsMethylation landscapeHistone modificationsDNA demethylationEpigenomic changesEarly reprogrammingEpigenetic regulatorsEpigenetic differencesDNA methylationHydroxymethylation analysisReprogrammingIncreased miR-155-5p and reduced miR-148a-3p contribute to the suppression of osteosarcoma cell death
Bhattacharya S, Chalk AM, Ng AJ, Martin TJ, Zannettino AC, Purton LE, Lu J, Baker EK, Walkley CR. Increased miR-155-5p and reduced miR-148a-3p contribute to the suppression of osteosarcoma cell death. Oncogene 2016, 35: 5282-5294. PMID: 27041566, DOI: 10.1038/onc.2016.68.Peer-Reviewed Original ResearchConceptsMiR-148aCell deathCell biological impactMiR-155-5p inhibitionCross-species comparisonsMiR-155-5pApoptosis/necroptosisNormal osteoblastsOS cellsOsteosarcoma cell deathMurine primary osteoblastsMiRNA expression patternsMiRNA-based therapiesCell fateMiR-155-5p overexpressionExpression patternsMolecular geneticsTractable targetsPrimary osteoblastsCandidate targetsBiological impactOsteoblast culturesRIPK1MiRNAsMiRNAThe microRNA miR-148a functions as a critical regulator of B cell tolerance and autoimmunity
Gonzalez-Martin A, Adams BD, Lai M, Shepherd J, Salvador-Bernaldez M, Salvador JM, Lu J, Nemazee D, Xiao C. The microRNA miR-148a functions as a critical regulator of B cell tolerance and autoimmunity. Nature Immunology 2016, 17: 433-440. PMID: 26901150, PMCID: PMC4803625, DOI: 10.1038/ni.3385.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisApoptosis Regulatory ProteinsAutoimmunityB-LymphocytesBcl-2-Like Protein 11Bone Marrow TransplantationCell Cycle ProteinsCell ProliferationDisease Models, AnimalHEK293 CellsHumansImmune ToleranceImmunoblottingLupus Erythematosus, SystemicMembrane ProteinsMiceMice, Inbred MRL lprMicroRNAsNuclear ProteinsProto-Oncogene ProteinsPTEN PhosphohydrolaseReverse Transcriptase Polymerase Chain ReactionSequence Analysis, RNAmiR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells
Lechman ER, Gentner B, Ng SW, Schoof EM, van Galen P, Kennedy JA, Nucera S, Ciceri F, Kaufmann KB, Takayama N, Dobson SM, Trotman-Grant A, Krivdova G, Elzinga J, Mitchell A, Nilsson B, Hermans KG, Eppert K, Marke R, Isserlin R, Voisin V, Bader GD, Zandstra PW, Golub TR, Ebert BL, Lu J, Minden M, Wang JC, Naldini L, Dick JE. miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells. Cancer Cell 2016, 29: 214-228. PMID: 26832662, PMCID: PMC4749543, DOI: 10.1016/j.ccell.2015.12.011.Peer-Reviewed Original ResearchConceptsLeukemia stem cellsMiR-126Human acute myeloid leukemia stem cellsAcute myeloid leukemia stem cellsMyeloid leukemia stem cellsPI3K/Akt/mTORMiR-126 expressionAkt/mTORMalignant hematopoietic stem cellsMiR-126 regulationStem cellsMiR-126 targetsLSC activityLSC quiescenceAML samplesChemotherapy resistanceHematopoietic stem cellsHematopoietic stem cell cyclingMiRNA signatureCell cycle progressionLSC functionCycle progressionStem cell cyclingSignature miRNAsCell cycling
2015
Hyperglycemia repression of miR-24 coordinately upregulates endothelial cell expression and secretion of von Willebrand factor
Xiang Y, Cheng J, Wang D, Hu X, Xie Y, Stitham J, Atteya G, Du J, Tang WH, Lee SH, Leslie K, Spollett G, Liu Z, Herzog E, Herzog RI, Lu J, Martin KA, Hwa J. Hyperglycemia repression of miR-24 coordinately upregulates endothelial cell expression and secretion of von Willebrand factor. Blood 2015, 125: 3377-3387. PMID: 25814526, PMCID: PMC4447857, DOI: 10.1182/blood-2015-01-620278.Peer-Reviewed Original ResearchConceptsVon Willebrand factorDiabetes mellitusMiR-24Diabetic patientsAdverse thrombotic eventsThrombotic cardiovascular eventsVWF expressionWillebrand factorDiabetic mouse modelNovel therapeutic targetHistamine H1 receptorsEndothelial cell expressionHyperglycemia-induced activationCardiovascular eventsThrombotic eventsH1 receptorsMouse modelVWF levelsTherapeutic targetCell expressionMellitusPatientsEndothelial cellsElevated levelsReactive oxygen speciesPharmacological modulation of the AKT/microRNA-199a-5p/CAV1 pathway ameliorates cystic fibrosis lung hyper-inflammation
Zhang PX, Cheng J, Zou S, D'Souza AD, Koff JL, Lu J, Lee PJ, Krause DS, Egan ME, Bruscia EM. Pharmacological modulation of the AKT/microRNA-199a-5p/CAV1 pathway ameliorates cystic fibrosis lung hyper-inflammation. Nature Communications 2015, 6: 6221. PMID: 25665524, PMCID: PMC4324503, DOI: 10.1038/ncomms7221.Peer-Reviewed Original ResearchConceptsCF macrophagesMiR-199aMicroRNA-199aHyper-inflammatory responseCFTR-deficient miceCystic fibrosis patientsCystic fibrosis lungLung destructionDisease morbidityPharmacological modulationCF miceCF lungFibrosis patientsInnate immunityLungMacrophagesCAV1 expressionDrug celecoxibReduced levelsTLR4CelecoxibMiceCav1PathwayMorbidityCharacterization of the mammalian miRNA turnover landscape
Guo Y, Liu J, Elfenbein SJ, Ma Y, Zhong M, Qiu C, Ding Y, Lu J. Characterization of the mammalian miRNA turnover landscape. Nucleic Acids Research 2015, 43: 2326-2341. PMID: 25653157, PMCID: PMC4344502, DOI: 10.1093/nar/gkv057.Peer-Reviewed Original ResearchConceptsMiRNA turnoverStable small RNAsMammalian cell typesCultured mammalian cellsSubset of miRNAsTurnover kineticsMiRNA biogenesisMost miRNAsMiR-222-5pNucleotide biasSmall RNAsMiRNA maturationMammalian cellsSame miRNAMiRNA poolExpression profilingHsp90 associationSequence determinantsDeep sequencingHsp90 inhibitionTurnover rateMiRNA isoformsDifferent turnover ratesSequence featuresCell typesmicroRNA Expression Profiling: Technologies, Insights, and Prospects
Roden C, Mastriano S, Wang N, Lu J. microRNA Expression Profiling: Technologies, Insights, and Prospects. Advances In Experimental Medicine And Biology 2015, 888: 409-421. PMID: 26663195, DOI: 10.1007/978-3-319-22671-2_21.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceCell Line, TumorDisease Models, AnimalGene Expression ProfilingGene Expression Regulation, NeoplasticHigh-Throughput Nucleotide SequencingHumansMicroRNAsMolecular Sequence DataNeoplasmsReverse Transcriptase Polymerase Chain ReactionSequence Homology, Nucleic AcidSignal TransductionConceptsLong small noncoding RNAsExpression profilingMiRNA isoformsMiRNA expressionProfiling technologiesDiverse biological processesSingle-cell variabilitySmall noncoding RNAsMiRNA profiling technologiesGlobal miRNA expressionNext-generation sequencingNoncoding RNAsCell variabilitySingle-molecule measurementsBiological functionsBiological processesTumor suppressorMicroRNA researchQuantitative RT-PCRCareful experimental designMiRNAsIsoformsRT-PCRProfilingExpression