miR-421通過下調FOXO1激活AKT-GSK-3β通路調控肺癌細胞增殖的研究.pdf

1、分類號：R446密級：不保密UDC：610學校代碼：11065博士專業(yè)學位論文miR421通過下調通過下調FOXO1激活激活AKTGSK3β通路調控肺癌細胞增殖的研究李化會指導教師孫桂榮教授通路調控肺癌細胞增殖的研究李化會指導教師孫桂榮教授學位類別專業(yè)學位專業(yè)領域臨床檢驗診斷學答辯日期學位類別專業(yè)學位專業(yè)領域臨床檢驗診斷學答辯日期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