1、分類號：R446密級：不保密UDC：610學(xué)校代碼：11065博士專業(yè)學(xué)位論文miR421通過下調(diào)通過下調(diào)FOXO1激活激活A(yù)KTGSK3β通路調(diào)控肺癌細(xì)胞增殖的研究李化會指導(dǎo)教師孫桂榮教授通路調(diào)控肺癌細(xì)胞增殖的研究李化會指導(dǎo)教師孫桂榮教授學(xué)位類別專業(yè)學(xué)位專業(yè)領(lǐng)域臨床檢驗(yàn)診斷學(xué)答辯日期學(xué)位類別專業(yè)學(xué)位專業(yè)領(lǐng)域臨床檢驗(yàn)診斷學(xué)答辯日期2015.5.26答辯委員會主席王傳新教授答辯委員會主席王傳新教授miR421promotestheprol

2、iferationoflungcancercellsbytargetingFOXO1activatingAKTGSK3βpasswayAbstractObjective:StudytheexpressionofmiR421inlungcancercelllineslungcancertissuespredictvalidatepotentialtargetgeneofmiR421investigatethefunctionitsmech

3、anismofmiR421intheproliferationoflungcancercellline.Methods:7kindsoflungcancercelllinesareroutinelyculturedlungcancertissuesareobtained.miR421expressioninabovespecimenisdetectedbyQPCR.WegainA549celllinesthatcanexpressmiR

4、421inhighlowlevelbyLiposometransfection.MTTclonefmationsoftagarareusedtotesttheeffectofmiR421onA549proliferation.TheproteinlevelsinAKTGSK3βpathwayarestudiedbyWesternblot.TargetgeneofmiR421ispredictedvalidatedbyTargetscan

5、Dualluciferasereptsystemrespectively.Results:miR421levelsinlungcancercelllineslungcancertissuesareveryhigher.ThelevelsinA549celllinelungcancertissuesareabout1132timeshigherthanthatinnegativecontrols(NC)respectively.miR42

6、1canpromotetheproliferation(5.720.02)clonefmation(2.590.10).InA549miR421cellslevelsofpAKT(1.230.01)pGSK3β(0.760.01)pRb(0.220.00)CyclinD1(0.700.03)arehigherthoseofFOXO1(0.050.00)p21(0.070.01)arelower.TargetscanpredictsFOX

7、O1maybeonetargetgeneofmiR421miR421canreducetherelativefluescence(0.330.13).Conclusions：miR421levelsinlungcancercelllineslungcancertissuesareveryhigherFmiR421promotestheproliferationoflungcancercellsbytargetingFOXO1activa