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
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 Research
2019
H19 lncRNA identified as a master regulator of genes that drive uterine leiomyomas
Cao T, Jiang Y, Wang Z, Zhang N, Al-Hendy A, Mamillapalli R, Kallen AN, Kodaman P, Taylor HS, Li D, Huang Y. H19 lncRNA identified as a master regulator of genes that drive uterine leiomyomas. Oncogene 2019, 38: 5356-5366. PMID: 31089260, PMCID: PMC6755985, DOI: 10.1038/s41388-019-0808-4.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphismsKey pathway genesGenome-scale studiesGenome-wide transcriptomeExtracellular matrixMethylation profiling analysisRegulation of expressionKey driver genesH19 single nucleotide polymorphismsEpigenetic modificationsMaster regulatorPathway genesTET expressionExpression changesExpression of H19H19 lncRNADriver genesProfiling analysisGenesH19Smooth muscle cellsUnifying mechanismMuscle cellsNovel target therapiesLncRNAs
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 role
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-adenosylmethionineH19 lncRNA alters stromal cell growth via IGF signaling in the endometrium of women with endometriosis
Ghazal S, McKinnon B, Zhou J, Mueller M, Men Y, Yang L, Mueller M, Flannery C, Huang Y, Taylor HS. H19 lncRNA alters stromal cell growth via IGF signaling in the endometrium of women with endometriosis. EMBO Molecular Medicine 2015, 7: 996-1003. PMID: 26089099, PMCID: PMC4551339, DOI: 10.15252/emmm.201505245.Peer-Reviewed Original ResearchConceptsChronic pelvic painReproductive-aged womenEndometrium of womenEndometrial stromal cellsStromal cell growthEndometrial preparationPelvic painEutopic endometriumAged womenEndometriosisNormal controlsStromal cellsH19 expressionImpact fertilityMolecular spongeH19/letNovel therapeuticsReduced proliferationInfertilityWomenEndometriumTurn inhibitsMicroRNA let-7Molecular mechanismsCell growth
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
2011
Genome‐Wide Studies Reveal That Lin28 Enhances the Translation of Genes Important for Growth and Survival of Human Embryonic Stem Cells
Peng S, Chen L, Lei X, Yang L, Lin H, Carmichael GG, Huang Y. Genome‐Wide Studies Reveal That Lin28 Enhances the Translation of Genes Important for Growth and Survival of Human Embryonic Stem Cells. Stem Cells 2011, 29: 496-504. PMID: 21425412, DOI: 10.1002/stem.591.Peer-Reviewed Original ResearchConceptsRNA helicase AHuman embryonic stem cellsEmbryonic stem cellsLin28-dependent stimulationTranslation of genesStem cellsLet-7 microRNADominant negative inhibitorPolysome profilingGenes ImportantRibosomal proteinsCellular mRNAsTarget genesDeep sequencingReporter analysisMetabolic enzymesLin28Cell growthExpression levelsGenesTranslationCellsGrowthImmunoprecipitationMicroRNAs
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 Research
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