人肝癌hepg2细胞α-13岩藻糖转移酶ⅳ基因靶向mirna干扰载体的构建及鉴定-construction and identification of mirna interference vector targeting α - 13 fucosyltransferase ⅳ gene in human hepatocellular carcinoma hepg 2 cells.docxVIP

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人肝癌hepg2细胞α-13岩藻糖转移酶ⅳ基因靶向mirna干扰载体的构建及鉴定-construction and identification of mirna interference vector targeting α - 13 fucosyltransferase ⅳ gene in human hepatocellular carcinoma hepg 2 cells.docx

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人肝癌hepg2细胞α-13岩藻糖转移酶ⅳ基因靶向mirna干扰载体的构建及鉴定-construction and identification of mirna interference vector targeting α - 13 fucosyltransferase ⅳ gene in human hepatocellular carcinoma hepg 2 cells

ConstructionandidentificationofmiRNAinterferencevectortargetingalpha-1,3fucosyltransferaseⅣgeneinHCCName:XiaoJun-qiSupervisor:ProfessorChenDeABSTRACTBackgroundsInworldwide,themortalityrateofHepatocellularcarcinoma(HCC)ranksthirdofallcancermortalityrate,anditisthesecondleadingcauseofdeathinChina.Thesurvivalrateiseffectivelyimprovedbycomprehensivetherapyincludingsurgicaltreatment,chemotherapyandothertreatments.Evenifradicalresection,the1-yearand3-yearrecurrenceratewere20%-64%and57%-81%.DuetometastasisandrecurrenceofHCC,itwillbedifficulttoimprovethesurvivalrateofHCCsignificantly.OvercomingthemetastasisandrecurrenceisakeypointinthetreatmentofHCC.TherearethreepathwaysoftheHCCmetastasis.Thecancercellstransfertoothersitesbybloodstream,lymphnodeandinvadingintoadjacentorgans.PreviousstudieshavedemonstratedthatHCCispronetointrahepaticmetastasisbyportalsystem.ThekeystepforintrahepaticmetastasisisadhesionofHCCcellstotheendothelialcellsofportalvein.Theα1,3-fucosyltransferase(FUT)proteinisakindofenzymeforsynthesisofSleXandLewisXinepithelialcells.ThefucosylationstepinSLeXsynthesiswascatalyzedbyFUT,aterminalglycosyltransferase.Theyhaveninesubtypes.SLeXantigensaresynthesizedbyFUT4.CancercellsandembryonictissuethatexpressSleXantigensontheircellsurfaceshavealsobeenknowntoadheretoendothelialE-selectinandareassociatedwithmalignancyandmetastasis.SleXantigenisthesmallestligandwiththreekindsofselectinprotein(E,L,P-selectin).SleXantigenisanadhesionmolecule,andexpressionofthisantigeningastrointestinalcancercells,coloniccancerandHCC.Itisreportedlycorrelatedwithtumorprogression,distantmetastasisandpostoperativerecurrence.Itisconfirmedbypathologicalexaminationthat64.10%ofHCCcanexpressSleXantigeninprimaryfoci.HigherpositiverateofSleXantigenarefoundinpathologicalexaminationsofthepatients’whohaveportalveintumorthrombus,extrahepaticmetastasis,satellitefocusandrecurrenceinthreemonthsaftersurgery.Duetothesecharacters,metastasisoftumorcellscanbeblockedbymonoclonalantibodiespreventingSleXantigenadhesio