2021
MMAB promotes negative feedback control of cholesterol homeostasis
Goedeke L, Canfrán-Duque A, Rotllan N, Chaube B, Thompson BM, Lee RG, Cline GW, McDonald JG, Shulman GI, Lasunción MA, Suárez Y, Fernández-Hernando C. MMAB promotes negative feedback control of cholesterol homeostasis. Nature Communications 2021, 12: 6448. PMID: 34750386, PMCID: PMC8575900, DOI: 10.1038/s41467-021-26787-7.Peer-Reviewed Original ResearchMeSH KeywordsAlkyl and Aryl TransferasesAnimalsCell Line, TumorCholesterolCholesterol, LDLFeedback, PhysiologicalGene Expression ProfilingHeLa CellsHep G2 CellsHomeostasisHumansHydroxymethylglutaryl CoA ReductasesLiverMice, Inbred C57BLMice, KnockoutPromoter Regions, GeneticReceptors, LDLRNA InterferenceSterol Regulatory Element Binding Protein 2ConceptsCholesterol biosynthesisCholesterol homeostasisMouse hepatic cell lineIntegrative genomic strategyIntricate regulatory networkMaster transcriptional regulatorCellular cholesterol levelsHMGCR activityLDL-cholesterol uptakeCholesterol levelsHuman hepatic cellsSterol contentGenomic strategiesTranscriptional regulatorsRegulatory networksIntracellular cholesterol levelsGene expressionUnexpected roleHepatic cell linesBiosynthesisMMABIntracellular levelsCell linesHomeostasisExpression of SREBP2Loss of hepatic miR-33 improves metabolic homeostasis and liver function without altering body weight or atherosclerosis
Price NL, Zhang X, Fernández-Tussy P, Singh AK, Burnap SA, Rotllan N, Goedeke L, Sun J, Canfrán-Duque A, Aryal B, Mayr M, Suárez Y, Fernández-Hernando C. Loss of hepatic miR-33 improves metabolic homeostasis and liver function without altering body weight or atherosclerosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2006478118. PMID: 33495342, PMCID: PMC7865172, DOI: 10.1073/pnas.2006478118.Peer-Reviewed Original ResearchConceptsMiR-33 deficiencyHDL-C levelsMiR-33Body weightAtherosclerotic plaque sizeAtherosclerotic plaque burdenDevelopment of fibrosisCholesterol transport capacityCholesterol transporter ABCA1High-density lipoprotein biogenesisSREBP2 transcription factorKnockout mouse modelConditional knockout mouse modelPlaque burdenCardiometabolic diseasesChow dietLiver functionMetabolic dysfunctionHDL metabolismHyperlipidemic conditionsMouse modelGlucose homeostasisCholesterol effluxLipid metabolismObesity
2017
Posttranscriptional regulation of lipid metabolism by non-coding RNAs and RNA binding proteins
Singh AK, Aryal B, Zhang X, Fan Y, Price NL, Suárez Y, Fernández-Hernando C. Posttranscriptional regulation of lipid metabolism by non-coding RNAs and RNA binding proteins. Seminars In Cell And Developmental Biology 2017, 81: 129-140. PMID: 29183708, PMCID: PMC5975105, DOI: 10.1016/j.semcdb.2017.11.026.Peer-Reviewed Original ResearchConceptsLipid metabolismNon-coding RNAImportance of microRNAsNumber of miRNAsRole of lncRNAsLipid-related genesTranscriptional regulationCoding RNAsPosttranscriptional regulationPosttranscriptional levelMiRNA expressionHigh abundanceLncRNAsRNACholesterol homeostasisMiR-33MiR-148aSpecific roleMiRNAsRegulationLipoprotein metabolismRecent findingsMetabolismProteinExpression
2013
Control of Cholesterol Metabolism and Plasma High-Density Lipoprotein Levels by microRNA-144
Ramírez CM, Rotllan N, Vlassov AV, Dávalos A, Li M, Goedeke L, Aranda JF, Cirera-Salinas D, Araldi E, Salerno A, Wanschel A, Zavadil J, Castrillo A, Kim J, Suárez Y, Fernández-Hernando C. Control of Cholesterol Metabolism and Plasma High-Density Lipoprotein Levels by microRNA-144. Circulation Research 2013, 112: 1592-1601. PMID: 23519695, PMCID: PMC3929583, DOI: 10.1161/circresaha.112.300626.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnticholesteremic AgentsApolipoprotein A-IATP Binding Cassette Transporter 1ATP-Binding Cassette TransportersChlorocebus aethiopsCholesterol, HDLCOS CellsDiet, High-FatGene Expression ProfilingHep G2 CellsHepatocytesHomeostasisHumansHydrocarbons, FluorinatedLiver X ReceptorsMacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutMicroRNAsOligonucleotide Array Sequence AnalysisOligonucleotidesOrphan Nuclear ReceptorsSulfonamidesConceptsAdenosine triphosphate-binding cassette transporter A1Liver X nuclear receptorCholesterol metabolismABCA1 expressionMiR-144HDL levelsLXR agonistsCholesterol effluxLXR ligandsHigh-density lipoprotein levelsPlasma high-density lipoprotein levelsTriphosphate-binding cassette transporter A1Potential therapeutical interventionsAtherosclerotic vascular diseaseMacrophage cholesterol effluxCassette transporter A1Cassette transporter G1MiR-144 expressionPrimary mouse peritoneal macrophagesHigh-density lipoprotein biogenesisEfflux of cholesterolFoam cell formationAdenosine triphosphate-binding cassette transportersModulation of miRNAsMiRNA expression signaturesMicroRNAs in Metabolic Disease
Fernández-Hernando C, Ramírez CM, Goedeke L, Suárez Y. MicroRNAs in Metabolic Disease. Arteriosclerosis Thrombosis And Vascular Biology 2013, 33: 178-185. PMID: 23325474, PMCID: PMC3740757, DOI: 10.1161/atvbaha.112.300144.BooksConceptsContribution of miRNAsCellular cholesterol exportMiR-33Fatty acid degradationSREBP genesIntronic miRNAMetabolic diseasesFatty acid synthesisHost genesCholesterol exportSpecific miRNAsPhysiological processesLipid homeostasisMiRNAsAcid synthesisAcid degradationCardiometabolic diseasesGenesMicroRNAsGlucose homeostasisCritical roleGlucose metabolismLipoprotein secretionRecent findingsMetabolic control
2011
miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling
Dávalos A, Goedeke L, Smibert P, Ramírez CM, Warrier NP, Andreo U, Cirera-Salinas D, Rayner K, Suresh U, Pastor-Pareja JC, Esplugues E, Fisher EA, Penalva LO, Moore KJ, Suárez Y, Lai EC, Fernández-Hernando C. miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 9232-9237. PMID: 21576456, PMCID: PMC3107310, DOI: 10.1073/pnas.1102281108.Peer-Reviewed Original ResearchConceptsFatty acid metabolismFatty acid oxidationMiR-33aInsulin receptor substrate 2Sirtuin 6Acid metabolismInsulin-signaling pathwayIntronic microRNAsSterol regulatory element-binding protein 2Acid oxidationHost genesKey enzymeHepatic cell linesMetabolic syndromeCarnitine palmitoyltransferase 1AMetabolic pathwaysSubstrate 2Cellular imbalanceProtein 2Cholesterol homeostasisGenesCell linesLevels of HDLPathwayMetabolism results
2010
MiR-33 Contributes to the Regulation of Cholesterol Homeostasis
Rayner KJ, Suárez Y, Dávalos A, Parathath S, Fitzgerald ML, Tamehiro N, Fisher EA, Moore KJ, Fernández-Hernando C. MiR-33 Contributes to the Regulation of Cholesterol Homeostasis. Science 2010, 328: 1570-1573. PMID: 20466885, PMCID: PMC3114628, DOI: 10.1126/science.1189862.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApolipoprotein A-IATP Binding Cassette Transporter 1ATP Binding Cassette Transporter, Subfamily G, Member 1ATP-Binding Cassette TransportersCarrier ProteinsCell LineCholesterolCholesterol, DietaryDietary FatsGene Expression RegulationHomeostasisHumansHypercholesterolemiaIntracellular Signaling Peptides and ProteinsIntronsLipoproteinsLipoproteins, HDLLiverMacrophagesMacrophages, PeritonealMembrane GlycoproteinsMiceMice, Inbred C57BLMicroRNAsNiemann-Pick C1 ProteinProteinsSterol Regulatory Element Binding Protein 2TransfectionConceptsSterol regulatory element-binding factor-2MiR-33Cellular cholesterol transportCholesterol effluxExpression of genesIntronic microRNAsTranscriptional regulatorsTriphosphate-binding cassette transportersAdenosine triphosphate-binding cassette transportersCellular cholesterol effluxCassette transportersHDL biogenesisHuman cellsCellular levelCholesterol homeostasisABCA1 expressionFactor 2Mouse macrophagesGenesLentiviral deliveryCholesterol transportExpressionABCA1Cholesterol metabolismEfflux
2006
Aplidin® induces JNK-dependent apoptosis in human breast cancer cells via alteration of glutathione homeostasis, Rac1 GTPase activation, and MKP-1 phosphatase downregulation
González-Santiago L, Suárez Y, Zarich N, Muñoz-Alonso M, Cuadrado A, Martínez T, Goya L, Iradi A, Sáez-Tormo G, Maier J, Moorthy A, Cato A, Rojas J, Muñoz A. Aplidin® induces JNK-dependent apoptosis in human breast cancer cells via alteration of glutathione homeostasis, Rac1 GTPase activation, and MKP-1 phosphatase downregulation. Cell Death & Differentiation 2006, 13: 1968-1981. PMID: 16543941, DOI: 10.1038/sj.cdd.4401898.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsApoptosisBreast NeoplasmsCalciumCell Cycle ProteinsCopperDepsipeptidesDown-RegulationDual Specificity Phosphatase 1Enzyme ActivationGlutathione DisulfideGlutathione PeroxidaseGlutathione ReductaseHeLa CellsHomeostasisHumansImmediate-Early ProteinsJNK Mitogen-Activated Protein KinasesMembrane PotentialsMiceMitochondrial MembranesOxidative StressPeptides, CyclicPhosphoprotein PhosphatasesProtein Phosphatase 1Protein Tyrosine PhosphatasesRac1 GTP-Binding ProteinReactive Oxygen SpeciesConceptsJun N-terminal kinaseJNK activationRac1 activationGlutathione homeostasisRac1 small GTPaseJNK-dependent apoptosisRac1 GTPase activationMitochondrial membrane potentialN-terminal kinaseMKP-1 phosphataseSmall GTPaseGTPase activationReactive oxygen speciesHuman breast cancer cellsGSSG/GSH ratioCell deathBreast cancer cellsRapid activationExogenous GSHRNA duplexesSustained activationGSH synthesisSpecific Rac1 inhibitorAplidinDownregulation of Rac1