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基于转录组学和代谢组学探究miR--497在小鼠NAFLD发病机制中的作用.docx

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基于转录组学和代谢组学探究miR--497在小鼠NAFLD发病机制中的作用 Title:ExploringtheRoleofmiR-497inthePathogenesisofNAFLDinMice:InsightsfromTranscriptomicsandMetabolomics Abstract: Non-alcoholicfattyliverdisease(NAFLD)isametabolicdisordercharacterizedbyexcessiveaccumulationoffatintheliverwithoutexcessivealcoholconsumption.AccumulatingevidencesuggeststhatmicroRNAs(miRNAs)playacrucialroleinthedevelopmentandprogressionofNAFLD.Amongthem,miR-497hasemergedasapotentialregulatorinNAFLDpathogenesis.ThisstudyaimstoexploretheroleofmiR-497inNAFLDusingtranscriptomicsandmetabolomicsapproachesinamousemodel. Introduction: NAFLDhasbecomeaglobalhealthconcernduetoitsincreasingprevalence,withnospecificpharmacologicaltreatmentsavailable.UnderstandingtheunderlyingmolecularmechanismsofNAFLDiscrucialfordevelopingeffectivetherapeuticstrategies.miRNAsaresmallnon-codingRNAmoleculesthatregulategeneexpressionatthepost-transcriptionallevelbybindingtothe3'-untranslatedregionoftargetmessengerRNAs(mRNAs).miRNAshavebeenimplicatedinvariousbiologicalprocesses,includinglipidmetabolismandinflammation. Methods: Inthisstudy,amousemodelofNAFLDwillbeestablishedbyfeedingmicewithahigh-fatdiet(HFD)foraspecifiedduration.LivertissuewillbecollectedforRNAextraction.Transcriptomicanalysiswillbeperformedusinghigh-throughputRNAsequencing,anddifferentialgeneexpressionanalysiswillbeconductedtoidentifymiR-497targetgenes.PathwayanalysiswillbeperformedtorevealthepotentialbiologicalprocessesandpathwaysaffectedbymiR-497.Additionally,metabolomicanalysiswillbeperformedtoexplorethealterationsinmetabolitesassociatedwithNAFLDprogression. Results: PreviousstudieshavesuggestedthatmiR-497levelsaredysregulatedinNAFLDpatientsaswellasinanimalmodels.OurtranscriptomicanalysiswillrevealthedownstreamtargetsofmiR-497thatareinvolvedinkeybiologicalprocessesrelatedtoNAFLD,suchaslipidmetabolism,inflammation,andoxidativestress.MetabolomicanalysiswillprovideinsightsintothemetabolicalterationsassociatedwithmiR-497dysregulation. Discussion: MiR-497hasbeenshowntoregulatelipid