OriginalArticleCharacterizationofcircRNA-Associated-ceRNANetworksinaSenescence-AcceleratedMouseProne8BrainShuaiZhang,1,2,3DinaZhu,1,2,3HongLi,1,2,3HejianLi,1,2,3ChengqiangFeng,1,2,3andWenshengZhang1,2,3,41BeijingAreaMajorLaboratoryofProtectionandUtilizationofTraditionalChineseMedicine,BeijingNormalUniversity,Beijing100088,China;2EngineeringResearchCenterofNaturalMedicine,MinistryofEducation,BeijingNormalUniversity,Beijing100088,China;3FacultyofGeographicalScience,CollegeofResourcesScience&Technology,BeijingNormalUniversity,Beijing100088,China;4National&LocalUnitedEngineeringResearchCenterforSanqiResourcesProtectionandUtilizationTechnology,Kunming650000,ChinaAlzheimer’sdisease(AD)isoneofthemostcommonneurode-generativediseases.AlthoughmanyresearchershaveattemptedtoexplaintheoriginsofAD,developinganeffectivestrategyinADclinicaltherapyisdifficult.RecentstudieshaverevealedapotentiallinkbetweenADandcircRNA-associated-ceRNAnetworks.However,fewgenome-widestudieshaveidentifiedthepotentialcircRNA-associated-ceRNApairsinvolvedinAD.Inthisstudy,wesystematicallyexploredthecircRNA-associated-ceRNAmechanismina7-month-oldsenescence-acceleratedmouseprone8(SAMP8)modelbrainthroughdeepRNAsequencing.Weobtained235significantlydysre-gulatedcircRNAtranscripts,30significantlydysregulatedmiRNAs,and1,202significantlydysregulatedmRNAs.WethenconstructedthemostcomprehensivecircRNA-associ-ated-ceRNAnetworksinSAMP8brain.GOanalysisrevealedthatthesenetworkswereinvolvedinregulatingthedevelop-mentofADfromvariousangles,forinstance,axonterminus(GO:0043679)andsynapse(GO:0045202).Followingrigorousselection,wediscoveredthatthecircRNA-associated-ceRNAnetworksinthisADmousemodelweremainlyinvolvedintheregulationofAbclearance(Hmgb2)andmyelinfunction(Dio2).Thisresearchisthefirsttoprovideasystematicdissec-tionofcircRNA-associated-ceRNAprofilinginSAMP8mousebrain.TheselectedcircRNA-associated-ceRNAnetworkscanprofoundlyaffectthediagnosisandtherapyofADinthefuture.INTRODUCTIONCircularRNA(circRNA)hasbecomearesearchf...
