Aldehyde Dehydrogenase-2 (ALDH2) Opposes Hepatocellular Carcinoma Progression by Regulating AMP-Activated Protein Kinase Signaling in Mice英文资料

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1、AMERICANASSOCIATIONFORTHESTUDYOFLIVERDISEASESHEPATOLOGY,VOL.65,NO.5,2017AldehydeDehydrogenase-2(ALDH2)OpposesHepatocellularCarcinomaProgressionbyRegulatingAMP-ActivatedProteinKinaseSignalinginMice1,2*1,5*3*1,521,511GuojunHou,LeiChen,GangLiu,LiangLi,YuanYang,He-XinYan,Hui-LuZhang,JingTang,111111,5

2、22YingChengYang,XimengLin,XinChen,GuijuanLuo,YanjingZhu,ShanhuaTang,JinZhang,HuiLiu,62432,51,5,7QingyangGu,Ling-HaoZhao,YixueLi,LeiLiu,WeipingZhou,andHongyangWangPotentialbiomarkersthatcanbeusedtodetermineprognosisandperformtargetedtherapiesareurgentlyneededtotreatpatientswithhepatocellularcarcin

3、oma(HCC).Tomeetthisneed,weperformedascreentoidentifyfunctionalgenesassociatedwithhepatocellularcarcinogenesisanditsprogressionatthetranscriptomeandproteomelevels.Weidentifiedaldehydededydrogenase-2(ALDH2)asageneofinterestforfurtherstudy.ALDH2levelsweresignificantlyloweratthemRNAandproteinlevelintum

4、ortissuesthaninnormaltissues,andtheywereevenlowerintissuesthatexhibitedincreasedmigratorycapacity.AstudyofclinicalassociationsshowedthatALDH2iscorrelatedwithsurvivalandmultiplemigration-associatedclinicopathologicaltraits,includingthepresenceofmetastasisandportalveintumorthrombus.Theresultofovere

5、xpressingorknockingdownALDH2showedthatthisgeneinhibitedmigrationandinvasionbothinvivoandinvitro.WealsofoundthatALDH2alteredtheredoxstatusofcellsbyregulatingacetaldehydelevelsandthatitfur-theractivatedtheAMP-activatedproteinkinase(AMPK)signalingpathway.Conclusion:DecreasedlevelsofALDH2mayindicatea

6、poorprognosisinHCCpatients,whileforcingtheexpressionofALDH2inHCCcellsinhibitedtheiraggres-sivebehaviorinvitroandinmicelargelybymodulatingtheactivityoftheALDH2-acetaldehyde-redox-AMPKaxis.Therefore,identifyingALDH2expressionlevelsinHCCmightbeausefulstrategyforclassifyingHCCpatientsandfordeveloping

7、potentialtherapeuticstrategiesthatspecificallytargetmetastaticHCC.(HEPATOLOGY2017;65:1628-1644).epatocellularcarcinoma(HCC)isthethird-hepaticresection,livertransplantation,andlocore-(4,5)mostfrequentcauseofcancer-relate