miR-200a-mediateddownregulationofZEB2andCTNNB1differentiallyinhibitsnasopharyngealcarcinomacellgrowth,migrationandinvasionHongpingXiaa,SamuelS.Nga,SongshanJiangb,WilliamK.C.Cheunga,JohnnySzea,Xiu-WuBianc,Hsiang-fuKungb,d,MarieC.Lina,*aIntegrativeChemicalBiologyLaboratory,InstituteofMolecularTechnology,DepartmentofChemistry,TheUniversityofHongKong,PokfulamRoad,HongKong,ChinabLaboratoryofIntegratedBioscience,SchoolofLifeSciences,SunYat-SenUniversity,Guangzhou,ChinacInstituteofPathologyandSouthwestCancerCenter,SouthwestHospital,ThirdMilitaryMedicalUniversity,Chongqing,ChinadStanleyHoCenterforEmergingInfectiousDiseases,LiKaShingInstituteofHealthScience,andStateKeyLaboratoryinOncologyinSouthChina,TheChineseUniversityofHongKong,Shatin,HongKong,ChinaarticleinfoArticlehistory:Received10November2009Availableonline24November2009Keywords:microRNANasopharyngealcarcinomaMigrationInvasionb-cateninabstractNasopharyngealcarcinoma(NPC),ahighlymetastaticandinvasivemalignanttumororiginatingfromthenasopharynx,iswidelyprevalentinSoutheastAsia,theMiddleEastandNorthAfrica.Althoughviral,die-taryandgeneticfactorshavebeenimplicatedinNPC,themolecularbasisofitspathogenesisisnotwelldefined.BasedonarecentmicroRNA(miRNA)microarraystudyshowingmiR-200downregulationinNPC,wefurtherinvestigatedtheroleofmiR-200ainNPCcarcinogenesis.WefoundthattheendogenousmiR-200aexpressionlevelincreaseswiththedegreeofdifferentiationinapanelofNPCcelllines,namelyundifferentiatedC666-1,high-differentiatedCNE-1,andlow-differentiatedCNE-2andHNE1cells.Byaseriesofgain-of-functionandloss-of-functionstudies,weshowedthatover-expressionofmiR-200ainhibitsC666-1cellgrowth,migrationandinvasion,whereasitsknock-downstimulatestheseprocessesinCNE-1cells.Inaddition,wefurtheridentifiedZEB2andCTNNB1asthefunctionaldownstreamtargetsofmiR-200a.Interestingly,knock-downofZEB2solelyimpededNPCcellmigrationandinvasion,whereasCTNNB1suppressiononlyinhibitedNPCcellgrowth,suggestingthattheinhibitoryeffectsofmiR-200aonNPCcellgrowth,migrationandinvas...
