2022
Impaired neurogenesis alters brain biomechanics in a neuroprogenitor-based genetic subtype of congenital hydrocephalus
Duy PQ, Weise SC, Marini C, Li XJ, Liang D, Dahl PJ, Ma S, Spajic A, Dong W, Juusola J, Kiziltug E, Kundishora AJ, Koundal S, Pedram MZ, Torres-Fernández LA, Händler K, De Domenico E, Becker M, Ulas T, Juranek SA, Cuevas E, Hao LT, Jux B, Sousa AMM, Liu F, Kim SK, Li M, Yang Y, Takeo Y, Duque A, Nelson-Williams C, Ha Y, Selvaganesan K, Robert SM, Singh AK, Allington G, Furey CG, Timberlake AT, Reeves BC, Smith H, Dunbar A, DeSpenza T, Goto J, Marlier A, Moreno-De-Luca A, Yu X, Butler WE, Carter BS, Lake EMR, Constable RT, Rakic P, Lin H, Deniz E, Benveniste H, Malvankar NS, Estrada-Veras JI, Walsh CA, Alper SL, Schultze JL, Paeschke K, Doetzlhofer A, Wulczyn FG, Jin SC, Lifton RP, Sestan N, Kolanus W, Kahle KT. Impaired neurogenesis alters brain biomechanics in a neuroprogenitor-based genetic subtype of congenital hydrocephalus. Nature Neuroscience 2022, 25: 458-473. PMID: 35379995, PMCID: PMC9664907, DOI: 10.1038/s41593-022-01043-3.Peer-Reviewed Original ResearchConceptsCongenital hydrocephalusCerebral ventricular dilatationPrimary defectNeuroepithelial cell differentiationRisk genesCerebrospinal fluid homeostasisWhole-exome sequencingNeuroepithelial stem cellsCortical hypoplasiaReduced neurogenesisVentricular dilatationVentricular enlargementCH mutationsPrenatal hydrocephalusDisease heterogeneityBrain surgeryCSF circulationHydrocephalusGenetic subtypesFluid homeostasisNeuroepithelial cellsNovo mutationsBrain transcriptomicsStem cellsCell differentiationPrecision analysis of mutant U2AF1 activity reveals deployment of stress granules in myeloid malignancies
Biancon G, Joshi P, Zimmer JT, Hunck T, Gao Y, Lessard MD, Courchaine E, Barentine AES, Machyna M, Botti V, Qin A, Gbyli R, Patel A, Song Y, Kiefer L, Viero G, Neuenkirchen N, Lin H, Bewersdorf J, Simon MD, Neugebauer KM, Tebaldi T, Halene S. Precision analysis of mutant U2AF1 activity reveals deployment of stress granules in myeloid malignancies. Molecular Cell 2022, 82: 1107-1122.e7. PMID: 35303483, PMCID: PMC8988922, DOI: 10.1016/j.molcel.2022.02.025.Peer-Reviewed Original Research
2021
Ultradeep sequencing differentiates patterns of skin clonal mutations associated with sun-exposure status and skin cancer burden
Wei L, Christensen SR, Fitzgerald ME, Graham J, Hutson ND, Zhang C, Huang Z, Hu Q, Zhan F, Xie J, Zhang J, Liu S, Remenyik E, Gellen E, Colegio OR, Bax M, Xu J, Lin H, Huss WJ, Foster BA, Paragh G. Ultradeep sequencing differentiates patterns of skin clonal mutations associated with sun-exposure status and skin cancer burden. Science Advances 2021, 7: eabd7703. PMID: 33523857, PMCID: PMC7775785, DOI: 10.1126/sciadv.abd7703.Peer-Reviewed Original ResearchConceptsSkin cancer riskCancer burdenCancer riskCutaneous squamous cell carcinomaNormal human skin samplesClonal mutationsCarcinogenic effectsSun-exposure statusSquamous cell carcinomaSkin cancer burdenCell carcinomaClonal cell growthNormal skinHuman skin samplesUV exposureUltradeep sequencingUV-induced mutationsSkin samplesCell growthSkinBurdenRiskMutationsExposureUV damage
2020
PIWIL1 promotes gastric cancer via a piRNA-independent mechanism
Shi S, Yang ZZ, Liu S, Yang F, Lin H. PIWIL1 promotes gastric cancer via a piRNA-independent mechanism. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 22390-22401. PMID: 32848063, PMCID: PMC7486755, DOI: 10.1073/pnas.2008724117.Peer-Reviewed Original ResearchConceptsPIWI-interacting RNAsPIWI proteinsGastric cancer cellsNonsense-mediated mRNA decay mechanismPiRNA-independent mechanismDomain protein familyMRNA decay mechanismMammalian somatic tissuesRNA deep sequencingGastric cancer cell line SNU-1Cancer cellsGastric cancer cell proliferationRNA pathwaysPPD proteinsProtein familyPiwil1 geneSomatic tissuesSomatic cancersCancer cell proliferationDeep sequencingRegulatory mechanismsOncogenic functionPIWIL1Gastric cancer tissuesDetectable functionDevelopment of a Brigatinib degrader (SIAIS117) as a potential treatment for ALK positive cancer resistance
Sun N, Ren C, Kong Y, Zhong H, Chen J, Li Y, Zhang J, Zhou Y, Qiu X, Lin H, Song X, Yang X, Jiang B. Development of a Brigatinib degrader (SIAIS117) as a potential treatment for ALK positive cancer resistance. European Journal Of Medicinal Chemistry 2020, 193: 112190. PMID: 32179332, DOI: 10.1016/j.ejmech.2020.112190.Peer-Reviewed Original ResearchMeSH KeywordsAnaplastic Lymphoma KinaseAntineoplastic AgentsCarcinoma, Non-Small-Cell LungCell Line, TumorCell ProliferationDose-Response Relationship, DrugDrug DevelopmentDrug Resistance, NeoplasmDrug Screening Assays, AntitumorHEK293 CellsHumansLung NeoplasmsMolecular Docking SimulationMolecular StructureProtein Kinase InhibitorsStructure-Activity RelationshipConceptsAnaplastic large cell lymphomaCell lung cancerLung cancerALK proteinNon-small cell lung cancerDrug resistanceSmall cell lung cancerLarge cell lymphomaPotential therapeutic strategyAnti-proliferation abilityCell linesNPM-ALK fusion proteinT cell linesCancer cell linesEML4-ALKCancer regressionTherapeutic strategiesPotential treatmentGrowth inhibition effectInhibitor drugsALK activityCancerCancer resistanceBrigatinibLymphoma
2019
Heat shock protein DNAJA1 stabilizes PIWI proteins to support regeneration and homeostasis of planarian Schmidtea mediterranea
Wang C, Yang ZZ, Guo FH, Shi S, Han XS, Zeng A, Lin H, Jing Q. Heat shock protein DNAJA1 stabilizes PIWI proteins to support regeneration and homeostasis of planarian Schmidtea mediterranea. Journal Of Biological Chemistry 2019, 294: 9873-9887. PMID: 31076507, PMCID: PMC6597837, DOI: 10.1074/jbc.ra118.004445.Peer-Reviewed Original ResearchConceptsPIWI proteinsPIWI-interacting RNA (piRNA) biogenesisPlanarian adult stem cellsHeat shock protein 40 family membersDifferent evolutionary lineagesPlanarian Schmidtea mediterraneaStem cell maintenanceStem cell regulationCo-immunoprecipitation assaysStem cellsSomatic stem cellsControl of proteinAdult stem cellsHuman gastric cancer cellsPiRNA biogenesisRNA biogenesisEvolutionary lineagesPiwi-like RNASchmidtea mediterraneaTwo-hybridSMEDWI-1Planarian speciesCell maintenanceGastric cancer cellsPlanarian regeneration
2018
miR-221/222 activate the Wnt/β-catenin signaling to promote triple-negative breast cancer
Liu S, Wang Z, Liu Z, Shi S, Zhang Z, Zhang J, Lin H. miR-221/222 activate the Wnt/β-catenin signaling to promote triple-negative breast cancer. Journal Of Molecular Cell Biology 2018, 10: 302-315. PMID: 30053090, DOI: 10.1093/jmcb/mjy041.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerWnt/β-cateninMiR-221/222 expressionTNBC cell linesBreast cancerMiR-221/222Β-cateninHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Progression of TNBCGrowth factor receptor 2Limited treatment optionsWnt/β-catenin activationNegative breast cancerFactor receptor 2Primary tumor samplesWnt/β-catenin signalingCell linesWnt3a treatmentMultiple negative regulatorsΒ-catenin activationΒ-catenin signalingPatient survivalPoor prognosisTreatment optionsNovel evidence for a PIWI-interacting RNA (piRNA) as an oncogenic mediator of disease progression, and a potential prognostic biomarker in colorectal cancer
Weng W, Liu N, Toiyama Y, Kusunoki M, Nagasaka T, Fujiwara T, Wei Q, Qin H, Lin H, Ma Y, Goel A. Novel evidence for a PIWI-interacting RNA (piRNA) as an oncogenic mediator of disease progression, and a potential prognostic biomarker in colorectal cancer. Molecular Cancer 2018, 17: 16. PMID: 29382334, PMCID: PMC5791351, DOI: 10.1186/s12943-018-0767-3.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overApoptosisBiomarkers, TumorCell DeathCell ProliferationColorectal NeoplasmsDisease ProgressionFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMaleMiddle AgedNeoplasm MetastasisNeoplasm StagingOncogenesPrognosisRNA InterferenceRNA, Small InterferingConceptsPIWI-interacting RNAsSmall RNA sequencingGene expression profiling resultsImportant epigenetic regulatorsDownstream target genesExpression profiling resultsCell survival pathwaysColorectal cancerPotential prognostic biomarkerTumor suppressor genePrognostic biomarkerEpigenetic regulatorsSequence complementarityNoncoding RNAsRNA sequencingTarget genesExpression profilingBiological functionsGene expressionSurvival pathwaysSuppressor geneClinical significanceDirect targetNovel oncogeneOncogenic mediators
2016
PIWI-Interacting RNAs in Gliomagenesis: Evidence from Post-GWAS and Functional Analyses
Jacobs DI, Qin Q, Lerro MC, Fu A, Dubrow R, Claus EB, DeWan AT, Wang G, Lin H, Zhu Y. PIWI-Interacting RNAs in Gliomagenesis: Evidence from Post-GWAS and Functional Analyses. Cancer Epidemiology Biomarkers & Prevention 2016, 25: 1073-1080. PMID: 27197292, DOI: 10.1158/1055-9965.epi-16-0047.Peer-Reviewed Original ResearchConceptsPIWI-interacting RNAsRole of piRNAsPIWI-piRNA pathwayFunctional analysisGenome-wide association studiesCell death/survivalExpression of genesTumor suppressive functionDeath/survivalGermline developmentPIWI proteinsGenetic association analysisGrowth-promoting propertiesInsertional mutationAssociation signalsAssociation studiesAssociation analysisIndex variantsGenetic variantsColony formationFunctional impactCell proliferationGlioma cell viabilityVariant allelesCell viabilityThe Role of PIWIL4, an Argonaute Family Protein, in Breast Cancer*
Wang Z, Liu N, Shi S, Liu S, Lin H. The Role of PIWIL4, an Argonaute Family Protein, in Breast Cancer*. Journal Of Biological Chemistry 2016, 291: 10646-10658. PMID: 26957540, PMCID: PMC4865913, DOI: 10.1074/jbc.m116.723239.Peer-Reviewed Original ResearchConceptsP-element-induced wimpy testisPIWI-interacting RNAsPIWI proteinsMDA-MB-231 cellsArgonaute family proteinsGermline developmentDiverse organismsWimpy testisFamily proteinsProteome analysisClass II proteinsPIWIL4Potential therapeutic targetStem cellsProteinMHC class II proteinsMigration abilityRNATherapeutic targetPIWIL4 expressionCancer tissuesBreast cancer tissuesCellsKey roleBiogenesisTudor-SN Interacts with Piwi Antagonistically in Regulating Spermatogenesis but Synergistically in Silencing Transposons in Drosophila
Ku HY, Gangaraju VK, Qi H, Liu N, Lin H. Tudor-SN Interacts with Piwi Antagonistically in Regulating Spermatogenesis but Synergistically in Silencing Transposons in Drosophila. PLOS Genetics 2016, 12: e1005813. PMID: 26808625, PMCID: PMC4726654, DOI: 10.1371/journal.pgen.1005813.Peer-Reviewed Original ResearchConceptsPiRNA biogenesisPrimordial germ cellsPiwi expressionTudor-SNSomatic cellsGerm cellsDiverse molecular functionsPost-transcriptional regulationEmbryonic somatic cellsPiwi mutantsDosage-dependent mannerGermline developmentPIWI proteinsMutant phenotypeMeiotic cytokinesisMolecular functionsSpliceosome assemblyPiwiEpigenetic programmingDiverse functionsBiological functionsAdult ovariesBiogenesisTransposonMale fertility
2015
Poreless eggshells
Lin H, Matzuk MM. Poreless eggshells. Journal Of Clinical Investigation 2015, 125: 4005-4007. PMID: 26485282, PMCID: PMC4639988, DOI: 10.1172/jci84692.Peer-Reviewed Original ResearchConceptsNuclear pore complex functionMissense mutationsSpecific amino acid changesAmino acid changesRecessive missense mutationSomatic cellsNucleoporin 107Human mutationsGenetic materialAcid changesExtragonadal functionsOvarian developmentOocyte developmentMutationsGenesSole sourceFemale genetic materialIntrinsic factorsComplex functionsOrthologsAbnormal ovarian developmentFollicular developmentEmbryosFliesOocytes
2014
Noncoding RNAs in the regulation of DNA replication
Ge XQ, Lin H. Noncoding RNAs in the regulation of DNA replication. Trends In Biochemical Sciences 2014, 39: 341-343. PMID: 25027733, PMCID: PMC4265214, DOI: 10.1016/j.tibs.2014.06.003.Peer-Reviewed Original ResearchPIWI proteins and PIWI-interacting RNAs in the soma
Ross RJ, Weiner MM, Lin H. PIWI proteins and PIWI-interacting RNAs in the soma. Nature 2014, 505: 353-359. PMID: 24429634, PMCID: PMC4265809, DOI: 10.1038/nature12987.Peer-Reviewed Original ResearchConceptsPIWI-interacting RNAsPIWI proteinsPIWI-piRNA pathwayDiscovery of millionsWhole-body regenerationStem cell functionSomatic functionsDiverse organismsLower eukaryotesGenome rearrangementsSomatic cellsEpigenetic programmingBiological rolePathwayRNAProteinRecent studiesEukaryotesTransposonOrganismsBiologyUnanticipated dimensionsFunctionCellsRearrangement
2013
Piwi Genes Are Dispensable for Normal Hematopoiesis in Mice
Nolde MJ, Cheng EC, Guo S, Lin H. Piwi Genes Are Dispensable for Normal Hematopoiesis in Mice. PLOS ONE 2013, 8: e71950. PMID: 24058407, PMCID: PMC3751959, DOI: 10.1371/journal.pone.0071950.Peer-Reviewed Original ResearchConceptsPiwi genesHematopoietic stem cellsNormal adult hematopoiesisPIWI protein familyStem cellsStem/progenitor cellsDiverse organismsAdult hematopoiesisProtein familyLong-term hematopoiesisMyeloablative stressCompetitive transplantationTransient expressionHuman leukemia cell linesHSC compartmentLeukemia cell linesGenesProliferative stateNormal hematopoiesisCell typesMIWI2Progenitor cellsLineage reconstitutionHematopoiesisCell proliferation
2012
High‐Efficiency Transfection and siRNA‐Mediated Gene Knockdown in Human Pluripotent Stem Cells
Ma Y, Lin H, Qiu C. High‐Efficiency Transfection and siRNA‐Mediated Gene Knockdown in Human Pluripotent Stem Cells. Current Protocols In Stem Cell Biology 2012, 21: 5c.2.1-5c.2.9. PMID: 22605647, DOI: 10.1002/9780470151808.sc05c02s21.Peer-Reviewed Original ResearchConceptsHigh transfection efficiencyPluripotent stem cellsTransfection efficiencyTransfection reagent Lipofectamine 2000Human embryonic stem cellsStem cellsHuman pluripotent stem cellsEmbryonic stem cellsPluripotent cell linesLipofectamine 2000SiRNA-mediated gene knockdownPluripotent cellsExpensive equipmentPluripotent genesGene knockdownProtocolEfficiencyPrimary cellsGenesCell linesCarriersCellsApplicationsTransfection
2011
The microRNA regulation of stem cells.
Huang X, Lin H. The microRNA regulation of stem cells. WIREs Mechanisms Of Disease 2011, 1: 83-95. PMID: 23801669, DOI: 10.1002/wdev.5.Peer-Reviewed Original ResearchUniting Germline and Stem Cells: The Function of Piwi Proteins and the piRNA Pathway in Diverse Organisms
Juliano C, Wang J, Lin H. Uniting Germline and Stem Cells: The Function of Piwi Proteins and the piRNA Pathway in Diverse Organisms. Annual Review Of Genetics 2011, 45: 447-469. PMID: 21942366, PMCID: PMC3832951, DOI: 10.1146/annurev-genet-110410-132541.Peer-Reviewed Original ResearchConceptsPIWI-interacting RNAsPIWI proteinsDiverse organismsStem cellsArgonaute protein familyPIWI-piRNA pathwayStem cell maintenanceSomatic stem/progenitor cellsAdult stem cellsStem/progenitor cellsPiRNA pathwayGermline specificationAnimal phylogenyGenome integrityProtein familyPosttranscriptional regulationCell maintenanceProtein bindsSomatic cellsEpigenetic programmingGermlineProgenitor cellsProteinOrganismsCommon mechanismGenome‐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 levelsGenesTranslationCellsGrowthImmunoprecipitationMicroRNAsMITOPLD Is a Mitochondrial Protein Essential for Nuage Formation and piRNA Biogenesis in the Mouse Germline
Watanabe T, Chuma S, Yamamoto Y, Kuramochi-Miyagawa S, Totoki Y, Toyoda A, Hoki Y, Fujiyama A, Shibata T, Sado T, Noce T, Nakano T, Nakatsuji N, Lin H, Sasaki H. MITOPLD Is a Mitochondrial Protein Essential for Nuage Formation and piRNA Biogenesis in the Mouse Germline. Developmental Cell 2011, 20: 364-375. PMID: 21397847, PMCID: PMC3062204, DOI: 10.1016/j.devcel.2011.01.005.Peer-Reviewed Original ResearchConceptsPiRNA biogenesisDerepression of retrotransposonsPrimary piRNA biogenesisSmall RNA biogenesisMutant germ cellsMitochondrial protein essentialMicrotubule-dependent localizationPiRNA pathwayDrosophila homologRNA biogenesisConserved roleMitoPLDDiverse speciesProtein essentialPerinuclear structuresMouse germlineOuter membraneBiogenesisGerm cellsMeiotic arrestPhospholipase DMetabolism/Phosphatidic acidMitochondriaMutant mice