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
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