Promoter Hypermethylation Mediated Downregulation of FBP1 in Human Hepatocellular Carcinoma and Colon Cancer 英文参考文献.docVIP

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Promoter Hypermethylation Mediated Downregulation of FBP1 in Human Hepatocellular Carcinoma and Colon Cancer 英文参考文献.doc

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Promoter Hypermethylation Mediated Downregulation of FBP1 in Human Hepatocellular Carcinoma and Colon Cancer 英文参考文献

PromoterHypermethylationMediatedDownregulation ofFBP1inHumanHepatocellularCarcinomaandColon Cancer MingquanChen1.,JianbinZhang2.,NingLi1,ZhipingQian1,MengqiZhu1,QianLi1,JianmingZheng1, XinyuWang1,GuangfengShi1* 1DepartmentofInfectiousDiseases,HuashanHospital,FudanUniversity,Shanghai,China,2SchoolofMedicine,InstituteofImmunology,ZhejiangUniversity,Hangzhou, China Abstract FBP1, fructose-1,6-bisphosphatase-1, a gluconeogenesis regulatory enzyme, catalyzes the hydrolysis of fructose 1,6- bisphosphatetofructose6-phosphateandinorganicphosphate.Themechanismthatitfunctionstoantagonizeglycolysis andwasepigeneticallyinactivatedthroughNF-kappaBpathwayingastriccancerhasbeenreported.However,itsroleinthe livercarcinogenesisstillremainsunknown.Here,weinvestigatedtheexpressionandDNAmethylationofFBP1inprimary HCCandcolontumor.FBP1waslowlyexpressedin80%(8/10)humanhepatocellularcarcinoma,66.7%(6/9)livercancercell linesand100%(6/6)coloncancercelllines,butwashigherinpairedadjacentnon-tumortissuesandimmortalizednormal celllines,whichwaswellcorrelatedwithitspromotermethylationstatus.MethylationwasfurtherdetectedinprimaryHCCs, gastric and colon tumor tissues, but none or occasionally in paired adjacent non-tumor tissues. Detailed methylation analysis of 29 CpG sites at a 327-bp promoter region by bisulfite genomic sequencing confirmed its methylation. FBP1 silencing could be reversed by chemical demethylation treatment with 5-aza-29-deoxycytidine (Aza), indicating direct epigenetic silencing. Restoring FBP1 expression in low expressed cells significantly inhibited cell growth and colony formationabilitythroughtheinductionofG2-Mphasecellcyclearrest.Moreover,theobservedeffectscoincidedwithan increaseinreactiveoxygenspecies(ROS)generation.Insummary,epigeneticinactivationofFBP1isalsocommoninhuman liverandcoloncancer.FBP1appearstobeafunctionaltumorsuppressorinvolvedintheliverandcoloncarcinogenesis. Citation:ChenM,ZhangJ,LiN,QianZ,ZhuM,etal.(2011)PromoterHypermethylationMediatedDownregulation