2024
TET3-overexpressing macrophages promote endometriosis
Lv H, Liu B, Dai Y, Li F, Bellone S, Zhou Y, Mamillapalli R, Zhao D, Venkatachalapathy M, Hu Y, Carmichael G, Li D, Taylor H, Huang Y. TET3-overexpressing macrophages promote endometriosis. Journal Of Clinical Investigation 2024, 134: e181839. PMID: 39141428, PMCID: PMC11527447, DOI: 10.1172/jci181839.Peer-Reviewed Original ResearchDisease-associated macrophagesTET3 overexpressionHuman endometriosis lesionsPathophysiology of endometriosisPro-inflammatory cytokine productionChronic inflammatory diseaseReproductive age womenEndometriosis lesionsE3 ubiquitin ligasePathogenic macrophagesCytokine productionEndometriosisInflammatory diseasesTET3 knockdownEndometriosis progressionPathogenic contributorsLet-7 miRNA expressionAge womenMacrophagesMouse macrophagesTherapeutic targetUbiquitin ligaseTET3MiceDiseaseRegulated circRNA nuclear export in neuronal differentiation
Li D, Huang Y. Regulated circRNA nuclear export in neuronal differentiation. Trends In Cell Biology 2024, 34: 620-621. PMID: 38964955, PMCID: PMC11316627, DOI: 10.1016/j.tcb.2024.06.005.Peer-Reviewed Original ResearchSkeletal 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
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 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
2017
112: Elevated hepatic gluconeogenesis by H19-mediated epigenetic regulation underlies altered metabolism in offspring prenatally exposed to metformin
Deng J, Geng T, Shen Y, Zhu L, Liu Y, Taylor H, Paidas M, Huang Y. 112: Elevated hepatic gluconeogenesis by H19-mediated epigenetic regulation underlies altered metabolism in offspring prenatally exposed to metformin. American Journal Of Obstetrics And Gynecology 2017, 216: s79. DOI: 10.1016/j.ajog.2016.11.1002.Peer-Reviewed Original Research
2016
161: H19 lncRNA alters trophoblast cell migration and invasion through TGF-β signaling in placentas with fetal growth restriction
Zuckerwise L, Lu L, Men Y, Li J, Buhimschi C, Buhimschi I, Bukowski R, Guller S, Paidas M, Huang Y. 161: H19 lncRNA alters trophoblast cell migration and invasion through TGF-β signaling in placentas with fetal growth restriction. American Journal Of Obstetrics And Gynecology 2016, 214: s103-s104. DOI: 10.1016/j.ajog.2015.10.197.Peer-Reviewed Original Research
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 disordersBiogenesisCellsKSRPPhosphorylationMicroRNAsThe noncoding RNAs H19 and let-7 alter IGF signaling and stromal cell growth in the endometrium of women with endometriosis
Ghazal S, McKinnon B, Zhou J, Mueller M, Flannery C, Huang Y, Taylor H. The noncoding RNAs H19 and let-7 alter IGF signaling and stromal cell growth in the endometrium of women with endometriosis. Fertility And Sterility 2014, 102: e5-e6. DOI: 10.1016/j.fertnstert.2014.07.025.Peer-Reviewed Original Research
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 tissuesH19 expression is increased in cumulus cells of PCOS patients undergoing IVF
Kallen A, Karakaya C, Seli E, Huang Y. H19 expression is increased in cumulus cells of PCOS patients undergoing IVF. Fertility And Sterility 2013, 100: s346. DOI: 10.1016/j.fertnstert.2013.07.873.Peer-Reviewed Original ResearchH19 expression is increased in cumulus cells of “high responder” women undergoing IVF, as compared to normal and low responders
Kallen A, Karakaya C, Seli E, Huang Y. H19 expression is increased in cumulus cells of “high responder” women undergoing IVF, as compared to normal and low responders. Fertility And Sterility 2013, 100: s343. DOI: 10.1016/j.fertnstert.2013.07.861.Peer-Reviewed Original Research