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1、中山大學(xué)博士學(xué)位論文miR.2l調(diào)控舌鱗癌細(xì)胞凋亡的實驗研究However,whatisthebiologymechanismforgeneregulationandexpressionchangeintheprocessofTSCC?Althoughnocertainresult,non·codingRNAs,especiallymicroRNAs(miRNAs),inspiretheresearchers.Itisknownthattumorigenesisreferstomultiplegenev
2、ariationandsinglegeneinterventioncannotinhabittumoranditsprogress.AsendogenousmiRNAcanregulateafeworhundredsgenes;besides,thosemiRNAsaremuchlessthanthecodinggenes,theyshouldbethestableandeffectiveanti—tumortargets.StudieshaveindicatedthatmiRNAsparticipat
3、einaseriallifeprocess,includinggrowth,hematopoiesis,organ—formation,apoptosis,cellproliferationandtumorigenesis.Theoncogeneoranti—oncogenemiRNAscorrelatewithcellproliferation,apoptosisanddifferentiation.Recently,highthroughputmicroarrayassayandquantitati
4、verealtimeRT-PCR(qRT-PCR)inresearchofcoloncancer,breastcancer,lungcancer,renalcancer,gastriccancer,lymphoma,leukemia,eta1.revealmiRNAsprofileofcancersandthechangesfromtheoriginallynormaltissues.Researchesindicatethattumors’malignancypositivelycorrelatedw
5、iththemiRNAchangeandinsomeadvancedcancer’certainmiRNAexpressionlevelsareevenlower.Inbreastcancer,miR一10b,let一7,miR一125bandmiR-145aredown-regulated,whilesomemiRNAsareup-regulated,likemiR一21andmiR一155.ThosealterationsofmiRNAsintumorsuggesttheeffectsofgener
6、egulation.ForheadandneckcancelparticularlytheTSCC,miRNAsandtheirfunctionsaleseldomstudied.WeemployedhighthroughputmicroarrayassaytoscreendifferentialexpressionofendogenousmiRNAsinTSCCtissuesofdifferentclinicalstagesandnormaltissue.ThenwefocusedonthemiR一2
7、1whichhassignificantlyhighexpressioninbothearlyandadvancedTSCC.Wecollected50independentsamplesofTSCCpatientsofdifferentclinicalstagesandusedqRT-PCRtotestifythedifferentialexpressionofmiR一21.Meanwhile,weusedimmunohistochemistrytechnologytodeterminetheexpr
8、essionoftropomyosin—I(TPM—1),thetargetofmiR一21,inthesame50samples.AndwedetectedcellapoptosisbyTunelapoptosisdetectionkit.Combinedwithpatients’clinicdata,weanalyzedtherelationshipamongthoseindexes.Basedonthoseresults—VIII—中