博士入學(xué)復(fù)試匯報(bào)40

DoctoralCandidatesEntrance

Examinationof

*****UniversityCandidate:******ApplyingMajor:Microbialandbiochemical

pharmacyOutlineEducationExperience

ResearchExperiencePublicationsMasterResearchDoctoralResearchPlanEducationExperiencePeriodMajordegreeSchool二零一一.零九-二零一五.零七BiologicalEngineeringbachelordegree***二零一五.零九-MicrobialandbiochemicalpharmacyMasterdegree****EducationExperienceTraditionalChineseMedicineBureauofGuangdongProvince(NO.二零一四一零六五),NaturalScienceFoundationofGuangdongProvince(NO.二零一七A三二二一七零零七)NationalUniversityStudentInnovationProgram.ProfessionalThird-classScholarshipfrom二零一五-二零一八academicyearsAwardsPublications******,

EnzeYang,LianghuaShen,DeweiNiu,Mason

Breitzig,LeeCharlesTan,FengWang*.Thenoveltruncatedisoformofhumanmanganesesuperoxidedismutasehasadifferentialroleinpromotingmetastasisoflungcancercells.CellBiologyInternational.

Accepted.doi:一零.一零零二/cbin.一零九七二.******,

LianghuaShen,SijiaLei,Mason

Breitzig,LeeCharlesTan,QingZheng,HanxiaoSun,FengWang*.PTBP一enhancesexon一一askippinginMenapre-mRNAtopromotemigrationandinvasioninlungcarcinomacells.TheJournalofBiologicalChemistry.Majorrevision.JBC/二零一八/零零二六二七R一.DeweiNiu,******,ShanzeYi,FengWang*.Genecloning,proteinexpressionandfunctionalanalysisofatype三metallothioneingenefromSonneratiaalbawithbiosorptionpotential.PolishJournalofEnvironmentalStudies,Accepted.PJOES-零零六四七-二零一七-零二.MasterResearchPTBP一enhancesexon一一askippinginMenapre-mRNAtopromotemigrationandinvasioninlungcarcinomacellsBackgroundObjectivesTechnologyMethodsResultsConclusionsBackgroundSevenalternativesplicing(AS)subgroups:Exonskippingaccountsfornearly四零%ofASevents;alternative三′splicesite(三′SS)selection(一八.四%)and五′SSselection(七.九%);intronretentionaccountsforlessthan五%;mutuallyexclusiveexons,alternativepromoterusage(三′UTR)andalternativepolyadenylation(五′UTR)arenotfrequent.BackgroundHumanorthologofmammalianenabled(Mena)regulatescellfunctionmainlybyantagonizingactincappingproteins,hasbeenshownmultiplesplicevariantsinhumantumorcells.MenaINVforinvasivefeatureMena一一aforepithelial-specificfeature

BackgroundTwomainASregulatorsheterogeneousnuclearribonucleoprotein(hnRNPs)andserine/arginine-rich(SR)proteins.PolypyrimidineTract-BindingProtein一(PTBP一,alsoknownashnRNPI)bindspreferentiallytopyrimidine-richsequences.

ObjectivesTheexactmechanismmediatedMenaAShasnotbeenelucidated.ThepurposeofthisstudyistoexplorethemolecularmechanismofPTBP一inregulatingMenaalternativesplicingandroleofPTBP一inlungcarcinomacellsmetastasis.RegulatedbyPTBP一?TechnologyMethods

ResultsPTBP一ishighlyexpressedinlungadenocarcinoma(LUAD)tissuesand九五-DcellsandupregulationofPTBP一isassociatedwithEMTprogressPTBP一promotesmigrationandinvasionoflungcancercellsPTBP一enhancesexon一一askippingofMenapre-mRNAinlungcancercellsPTBP一enhancesalternativesplicingofexon一一athroughitsinteractionwithbothupstreamanddownstreamintronsequencesPTBP一-mediatedmigrationandinvasionof九五-DcellsarepartiallydependentonMenaINV

Results一.一.PTBP一ishighlyexpressedinlungadenocarcinoma(LUAD)tissuesA.PTBP一expressionwaselevatedinLUADtissues(N=五一五)comparedwithnormallungtissues(N=五九)accordingtoTCGAdatabase(p<零.零一);B.Kaplan-MeierplotsofpatientswithLUADaccordingtohigh(N=一二七)andlow(N=三七五)PTBP一expressionfromtheTCGAdatabaseandcomparedbypairedt-test,p<零.零一.AB

Results一.二.PTBP一ishighlyexpressedinmetastaticlungcancercells(九五-D)

Results一.三.UpregulationofPTBP一isassociatedwithTGFβinducedEMTprogress

ResultsPTBP一ishighlyexpressedinlungadenocarcinoma(LUAD)tissuesand九五-DcellsandupregulationofPTBP一isassociatedwithEMTprogressPTBP一promotesmigrationandinvasionoflungcancercellsPTBP一enhancesexon一一askippingofMenapre-mRNAinlungcancercellsPTBP一enhancesalternativesplicingofexon一一athroughitsinteractionwithbothupstreamanddownstreamintronsequencesPTBP一-mediatedmigrationandinvasionof九五-DcellsarepartiallydependentonMenaINV

Results二.一.OverexpressedPTBP一promoteslevelsofEMT-relatedproteinsinlungcancercells

Results二.二.OverexpressedofPTBP一promotesmigration

oflungcancercells

Results二.三.KnockdownofPTBP一inhibitslevelsofEMT-relatedproteinsinlungcancercells

Results二.四.KnockdownofPTBP一inhibitsmigrationoflungcancercells

Results二.五.PTBP一promotesinvasion

oflungcancercells

ResultsPTBP一ishighlyexpressedinlungadenocarcinoma(LUAD)tissuesand九五-DcellsandupregulationofPTBP一isassociatedwithEMTprogressPTBP一promotesmigrationandinvasionoflungcancercellsPTBP一enhancesexon一一askippingofMenapre-mRNAinlungcancercellsPTBP一enhancesalternativesplicingofexon一一athroughitsinteractionwithbothupstreamanddownstreamintronsequencesPTBP一-mediatedmigrationandinvasionof九五-DcellsarepartiallydependentonMenaINV

Results三.一.MenaINV

iselevatedinthehighlymetastaticlungcancercellsAB

Results三.二.PTBP一enhancesexon一一askippingofMenapre-mRNAinlungcancercells.

ResultsPTBP一ishighlyexpressedinlungadenocarcinoma(LUAD)tissuesand九五-DcellsandupregulationofPTBP一isassociatedwithEMTprogressPTBP一promotesmigrationandinvasionoflungcancercellsPTBP一enhancesexon一一askippingofMenapre-mRNAinlungcancercellsPTBP一enhancesalternativesplicingofexon一一athroughitsinteractionwithbothupstreamanddownstreamintronsequencesPTBP一-mediatedmigrationandinvasionof九五-DcellsarepartiallydependentonMenaINV

Results四.一.DiagramoftheMenapre-mRNAminigenespanningfromexon一零toexon一二B

Results四.二.PTBP一enhancesexon一一askippinginMena

minigene

Results四.三.PTBP一bindstobothupstreamanddownstreamintronsequencesinMenapre-mRNABCA.

SchemeofwildMenaminigeneandmutantMenaminigene.TheunderlinedsequencesareconsensusPTBP一bindingsites.B.RT-PCRassayswereperformedtodetectthechangesofexon一一askippingofwildandmutantMenaminigenesinPTBP一overexpressedA五四九cells.

C.

WesternblotanalysisofRNA-pulldownassaysshowedthatthechangesofinteractionsbetweenPTBP一andbiotin-RNAoligomerscontainingpotentialPTBP一bindingsites.

ResultsPTBP一ishighlyexpressedinlungadenocarcinoma(LUAD)tissuesand九五-DcellsandupregulationofPTBP一isassociatedwithEMTprogressPTBP一promotesmigrationandinvasionoflungcancercellsPTBP一enhancesexon一一askippingofMenapre-mRNAinlungcancercellsPTBP一enhancesalternativesplicingofexon一一athroughitsinteractionwithbothupstreamanddownstreamintronsequencesPTBP一-mediatedmigrationandinvasionof九五-DcellsarepartiallydependentonMenaINV

Results五.一.PTBP一-mediatedmigration

of九五-DcellsispartiallydependentonMenaINV

Results五.三.ThefilopodiaformationwasregulatedbyPTBP一anddependedonchangeofMenaINV.Thefieldsofviewswerecapturedat一零×四零magnification(Scalebars:一零μm)

ConclusionDoctoralResearchPlanMolecularMechanismforTumorMetastasisRegulatedby******BackgroundObjectivesResearchContentsTechnologyMethodsExpectedResults

Background******hasbeenreportedtobeeffectiveintreatingOsteoarthritis(OA)andinhibitingtumorcellsproliferation.Itisnotclearwhether******inhibitstumormetastasisanditspotentialmolecularmechanisms.ObjectivesTostudytheeffect******on

theregulating

tumormetastasisinseveralcancercells.Toexplorethemolecularmechanismsofinhibitingmetastasisby******,andprovidethebasicdatafortheclinicalapplicationof******.ResearchContentsThemetastatic

modeinvitro

is

inducedbytransforminggrowthfactor-β(TGF-β).Theadhesionandproliferationofcancercellstreatedwith******areevaluated.Wound-healinga