2024
Skeletal muscle TET3 promotes insulin resistance through destabilisation of PGC-1α
Liu B, Xie D, Huang X, Jin S, Dai Y, Sun X, Li D, Bennett A, Diano S, Huang Y. Skeletal muscle TET3 promotes insulin resistance through destabilisation of PGC-1α. Diabetologia 2024, 67: 724-737. PMID: 38216792, PMCID: PMC10904493, DOI: 10.1007/s00125-023-06073-5.Peer-Reviewed Original ResearchConceptsTen-eleven translocationMuscle insulin sensitivityRNA-seqPGC-1aRegulation of muscle insulin sensitivityType 2 diabetesAnalysis of RNA-seqResponse to environmental cuesGenome-wide expression profilingWild-typeHFD-fedHFD-induced insulin resistanceHigh-fat diet (HFD)-inducedExpression levelsMaintenance of glucoseSkeletal muscle insulin sensitivityAccession numbersSkeletal muscleEnhanced glucose toleranceFamily dioxygenasesMitochondrial respirationSkeletal muscle of humansEnvironmental cuesMitochondrial functionBiological processes
2023
Let-7 suppresses liver fibrosis by inhibiting hepatocyte apoptosis and TGF-β production
Song J, Lv H, Liu B, Hao M, Taylor H, Zhang X, Li D, Huang Y. Let-7 suppresses liver fibrosis by inhibiting hepatocyte apoptosis and TGF-β production. Molecular Metabolism 2023, 78: 101828. PMID: 37898449, PMCID: PMC10641683, DOI: 10.1016/j.molmet.2023.101828.Peer-Reviewed Original ResearchConceptsFas-mediated apoptosisLet-7Hepatocyte apoptosisNegative feedback loopMouse primary hepatocytesLet-7 miRNAsTGF-b signalingSignaling networksApoptosis of hepatocytesTransient transfectionFas expressionInhibiting hepatocyte apoptosisSiRNA knockdownLet-7 expressionLet-7 overexpressionMouse modelApoptosisPrimary hepatocytesSuppressed hepatocyte apoptosisTET3Liver fibrosisFeedback loopExpressionDriver of liver fibrosisAdeno-associated viral vectorsA small-molecule degrader of TET3 as treatment for anorexia nervosa in an animal model
Lv H, Catarino J, Li D, Liu B, Gao X, Horvath T, Huang Y. A small-molecule degrader of TET3 as treatment for anorexia nervosa in an animal model. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2300015120. PMID: 37036983, PMCID: PMC10120042, DOI: 10.1073/pnas.2300015120.Peer-Reviewed Original ResearchConceptsVesicular GABA transporterActivity-based anorexiaExpression of AgRPNeuropeptide YAgRP neuronsAnorexia nervosaAnxiety/depressive-like behaviorsHypothalamic AgRP neuronsDepressive-like behaviorCurrent treatment optionsHigh relapse rateStress-related disordersHuman neuronal cellsNutritional supportRelapse rateTreatment optionsAnxiolytic effectsPsychiatric illnessMouse modelAnimal modelsHigh mortalityGABA transporterGenetic ablationNeuronal cellsNeurons
2022
Let-7 underlies metformin-induced inhibition of hepatic glucose production
Xie D, Chen F, Zhang Y, Shi B, Song J, Chaudhari K, Yang SH, Zhang GJ, Sun X, Taylor HS, Li D, Huang Y. Let-7 underlies metformin-induced inhibition of hepatic glucose production. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2122217119. PMID: 35344434, PMCID: PMC9169108, DOI: 10.1073/pnas.2122217119.Peer-Reviewed Original ResearchConceptsHepatic glucose productionAntidiabetic effectsMouse modelGlucose productionPotent antidiabetic actionsHepatocyte nuclear factor 4 alphaNuclear factor 4 alphaFunction mouse modelsHuman primary hepatocytesMetformin-induced inhibitionAntidiabetic actionTherapeutic effectGlucose homeostasisSuprapharmacological concentrationsRelevant dosesHepatic deliveryMetforminFetal isoformsPotential therapeuticsPrimary hepatocytesMost studiesLet-7Regulatory pathwaysHyperglycemiaDiabetes
2020
A Positive Feedback Loop of TET3 and TGF-β1 Promotes Liver Fibrosis
Xu Y, Sun X, Zhang R, Cao T, Cai SY, Boyer JL, Zhang X, Li D, Huang Y. A Positive Feedback Loop of TET3 and TGF-β1 Promotes Liver Fibrosis. Cell Reports 2020, 30: 1310-1318.e5. PMID: 32023451, PMCID: PMC7063678, DOI: 10.1016/j.celrep.2019.12.092.Peer-Reviewed Original ResearchHepatic TET3 contributes to type-2 diabetes by inducing the HNF4α fetal isoform
Da Li, Cao T, Sun X, Jin S, Di Xie, Huang X, Yang X, Carmichael GG, Taylor HS, Diano S, Huang Y. Hepatic TET3 contributes to type-2 diabetes by inducing the HNF4α fetal isoform. Nature Communications 2020, 11: 342. PMID: 31953394, PMCID: PMC6969024, DOI: 10.1038/s41467-019-14185-z.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDiabetes Mellitus, Type 2DioxygenasesDisease Models, AnimalDNA DemethylationDNA MethylationDNA-Binding ProteinsFastingGene Expression RegulationGlucagonGlucoseHepatocyte Nuclear Factor 3-betaHepatocyte Nuclear Factor 4LiverMaleMiceMice, Inbred C57BLMice, KnockoutPromoter Regions, GeneticProtein IsoformsTranscriptional ActivationTranscriptomeUp-RegulationConceptsHepatic glucose productionType 2 diabetesGlucose homeostasisAdult liverSystemic glucose homeostasisPotential therapeutic targetGenetic mouse modelsFetal versionKey gluconeogenic genesMouse modelTherapeutic targetHNF4α functionGlucose productionFetal isoformsLiverT2D.DiabetesPromoter demethylationGluconeogenic genesTET3 overexpressionHNF4αHomeostasisTET3Regulatory mechanismsIsoforms
2018
H19 lncRNA Promotes Skeletal Muscle Insulin Sensitivity in Part by Targeting AMPK
Geng T, Liu Y, Xu Y, Jiang Y, Zhang N, Wang Z, Carmichael GG, Taylor HS, Li D, Huang Y. H19 lncRNA Promotes Skeletal Muscle Insulin Sensitivity in Part by Targeting AMPK. Diabetes 2018, 67: db180370. PMID: 30201684, PMCID: PMC6198334, DOI: 10.2337/db18-0370.Peer-Reviewed Original ResearchConceptsMuscle insulin sensitivityEnergy sensor AMPKUnknown physiological functionImportant downstream effectorWhole-body energy metabolismCellular energy sensor AMPKEpigenetic mechanismsMuscle insulin resistanceDownstream effectorsAMPK activationMitochondrial biogenesisSystemic glucose homeostasisSkeletal muscle insulin sensitivityPhysiological functionsImportant regulatorAMPKInsulin-resistant human subjectsDUSP27Energy metabolismH19H19 expressionMuscle cellsSkeletal muscleGlucose uptakePivotal roleElevated hepatic expression of H19 long noncoding RNA contributes to diabetic hyperglycemia
Zhang N, Geng T, Wang Z, Zhang R, Cao T, Camporez JP, Cai SY, Liu Y, Dandolo L, Shulman GI, Carmichael GG, Taylor HS, Huang Y. Elevated hepatic expression of H19 long noncoding RNA contributes to diabetic hyperglycemia. JCI Insight 2018, 3: e120304. PMID: 29769440, PMCID: PMC6012507, DOI: 10.1172/jci.insight.120304.Peer-Reviewed Original ResearchConceptsHepatic glucose productionGenome-wide methylationExpression of Hnf4aGluconeogenic transcription factorsDiabetic hyperglycemiaH19 depletionTranscriptome analysisTranscription factorsExpression of H19Molecular mechanismsDiet-induced diabetic miceExcessive hepatic glucose productionType 2 diabetesInsulin-dependent suppressionElevated hepatic expressionH19 knockdownH19Promoter methylationMechanistic explanationMethylationDiabetic patientsRNADiabetic miceInsulin resistanceH19 overexpression
2015
H19 lncRNA alters DNA methylation genome wide by regulating S-adenosylhomocysteine hydrolase
Zhou J, Yang L, Zhong T, Mueller M, Men Y, Zhang N, Xie J, Giang K, Chung H, Sun X, Lu L, Carmichael GG, Taylor HS, Huang Y. H19 lncRNA alters DNA methylation genome wide by regulating S-adenosylhomocysteine hydrolase. Nature Communications 2015, 6: 10221. PMID: 26687445, PMCID: PMC4703905, DOI: 10.1038/ncomms10221.Peer-Reviewed Original ResearchConceptsS-adenosylhomocysteine hydrolaseCellular componentsDNA methylation genomeGenome-wide methylation profilingOnly mammalian enzymeNumerous gene lociS-adenosylhomocysteineMode of regulationDiverse cellular componentsMethylation genomeMammalian developmentMethylation dynamicsIgf2-H19Mammalian enzymeRegulatory circuitsDNA methylationDependent methyltransferasesMethylation changesMethylation profilingPotent feedback inhibitorEpigenetic alterationsGene locusH19 lncRNAFeedback inhibitorS-adenosylmethionine
2014
The H19/let-7 double-negative feedback loop contributes to glucose metabolism in muscle cells
Gao Y, Wu F, Zhou J, Yan L, Jurczak MJ, Lee HY, Yang L, Mueller M, Zhou XB, Dandolo L, Szendroedi J, Roden M, Flannery C, Taylor H, Carmichael GG, Shulman GI, Huang Y. The H19/let-7 double-negative feedback loop contributes to glucose metabolism in muscle cells. Nucleic Acids Research 2014, 42: 13799-13811. PMID: 25399420, PMCID: PMC4267628, DOI: 10.1093/nar/gku1160.Peer-Reviewed Original ResearchConceptsDouble-negative feedback loopLet-7PI3K/Akt-dependent phosphorylationLet-7 targetsHuman genetic disordersAkt-dependent phosphorylationMuscle cellsInsulin-resistant rodentsSponge lncRNAsMolecular spongeH19 lncRNAFeedback loopGrowth controlDepletion resultsH19Impaired insulinLncRNAsTarget miRNAGlucose uptakeGenetic disordersBiogenesisCellsKSRPPhosphorylationMicroRNAs
2013
The Imprinted H19 LncRNA Antagonizes Let-7 MicroRNAs
Kallen AN, Zhou XB, Xu J, Qiao C, Ma J, Yan L, Lu L, Liu C, Yi JS, Zhang H, Min W, Bennett AM, Gregory RI, Ding Y, Huang Y. The Imprinted H19 LncRNA Antagonizes Let-7 MicroRNAs. Molecular Cell 2013, 52: 101-112. PMID: 24055342, PMCID: PMC3843377, DOI: 10.1016/j.molcel.2013.08.027.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesCell DifferentiationComputational BiologyDatabases, GeneticGene Expression ProfilingGene Expression RegulationGenomic ImprintingGenotypeHEK293 CellsHuman Umbilical Vein Endothelial CellsHumansMiceMicroRNAsMuscle DevelopmentMyoblasts, SkeletalPhenotypeRibonucleoproteinsRNA InterferenceRNA, Long NoncodingTime FactorsTransfectionConceptsLet-7 familyWide transcriptome analysisHuman genetic disordersNoncanonical binding siteLet-7 microRNALet-7 overexpressionGene functionH19 depletionTranscriptome analysisMuscle differentiationMolecular spongeUnexpected modeImportant regulatorAdult muscleH19 knockdownRecent implicationMiR-675Physiological significanceMicroRNAsH19Binding sitesGenetic disordersOverexpressionImportant roleFetal tissues
2001
Splicing Factors SRp20 and 9G8 Promote the Nucleocytoplasmic Export of mRNA
Huang Y, Steitz J. Splicing Factors SRp20 and 9G8 Promote the Nucleocytoplasmic Export of mRNA. Molecular Cell 2001, 7: 899-905. PMID: 11336712, DOI: 10.1016/s1097-2765(01)00233-7.Peer-Reviewed Original ResearchNucleocytoplasmic mRNA Transport
Huang Y, Carmichael G. Nucleocytoplasmic mRNA Transport. Results And Problems In Cell Differentiation 2001, 34: 139-155. PMID: 11288673, DOI: 10.1007/978-3-540-40025-7_9.Peer-Reviewed Original ResearchConceptsMRNA exportMRNA transportMature mRNA moleculesMRNA nuclear exportViral model systemNuclear pore complexRNA polymerase IIMessenger RNA precursorsFundamental biological processesNucleocytoplasmic mRNA transportRemoval of intronsPolymerase IIPore complexNuclear exportRNA precursorsMRNA moleculesBiological processesProcessing reactionsModel systemCytoplasmDetailed mechanismIntronsPolyadenylationSplicingExport
1999
Intronless mRNA transport elements may affect multiple steps of pre‐mRNA processing
Huang Y, Wimler K, Carmichael G. Intronless mRNA transport elements may affect multiple steps of pre‐mRNA processing. The EMBO Journal 1999, 18: 1642-1652. PMID: 10075934, PMCID: PMC1171251, DOI: 10.1093/emboj/18.6.1642.Peer-Reviewed Original Research
1997
The mouse histone H2a gene contains a small element that facilitates cytoplasmic accumulation of intronless gene transcripts and of unspliced HIV-1-related mRNAs
Huang Y, Carmichael G. The mouse histone H2a gene contains a small element that facilitates cytoplasmic accumulation of intronless gene transcripts and of unspliced HIV-1-related mRNAs. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 10104-10109. PMID: 9294170, PMCID: PMC23318, DOI: 10.1073/pnas.94.19.10104.Peer-Reviewed Original Research