缺氧诱导因子

12Exercisetrainingstimulatesischemia-inducedneovascularizationviaphosphatidylinositol3-kinase/Akt-dependenthypoxia-inducedfactor-1alphareactivationinmiceofadvancedage.在老年小鼠中通过磷脂酰肌醇3激酶/Akt依赖的缺氧因子1α活化运动训练刺激缺血诱导的血管新生因子18、TranscriptionalregulationofBNIP3bySp3inprostatecancer.BNIP3通过SP3在前列腺癌中的转录调控。Keywords:prostatecancer;Sp3;BNIP3;transcriptionalregulation;proliferationBACKGROUNDThetranscriptionfactorsSp3/Sp1areexpressedinavarioustypesofcancersandBNIP3isoverexpressedinprostatecancer.AlthoughithasbeendemonstratedthatBNIP3istranscriptionallyregulatedbyHIF-1αandispost-transcriptionallyregulatedbymiR145,ourpreviousdataindicatedthattheremightbesomeothertranscriptionfactorsregulatingBNIP3inprostatecancer.ThisstudyisconductedtoinvestigatewhetherBNIP3expressionisdirectlyregulatedbySp3/Sp1ornot.转录因子SP1SP3/在各种类型的癌症和BNIP3的表达在前列腺癌中高表达。虽然它已被证明是αBNIP3HIF-1的转录调节，后由miR145转录调控，我们以前的数据表明，可能有一些其他的转录调节因子在前列腺癌中的表达。本研究旨在探讨BNIP3的表达是由sp3/SP1或不能直接调节MATERIALSANDMETHODSBioinformaticsanalysisshowsthatBNIP3promotercontainsseveralpotentialSp3/Sp1bindingsites.AndthenitisdemonstratedthatSP3couldregulatetheBNIP3transcriptionallybybindingtothepredictedsitesbydualreportergeneassays,ChIP,andEMSA.ThebiologicaleffectsofSP3regulatingBNIP3onprostatecancercellsproliferationaremeasuredbyMTT,TUNEL,andflowcytometry.生物信息学分析表明，BNIP3启动子包含了几个潜在的sp3/Sp1结合位点。然后，它表明SP3可以调节转录结合BNIP3的预测双报告基因检测，芯片网站，EMSA。SP3调控BNIP3对前列腺癌细胞增殖的生物学效应是通过MTT法、TUNEL法和流式细胞仪检测。RESULTSOurdatashowthatSp3butnotSp1,ispositivelyrelatedtoBNIP3overexpressioninprostatecancer.Sp3candirectlyregulateBNIP3transcriptionbymainlybindingtotheSp3bindingsites(−624∼−615and−350∼−343)ofBNIP3promoter.KnockdownofSp3byRNAinterferencecouldreducecellsgrowthandleadtocellsapoptosisinPC-3andDU145.Sp3-dependentBNIP3overexpressionmightbeanimportantmechanismtopromoteprostatecancercellsproliferation.CONCLUSIONThisisthefirststudytoprovidedirectevidenceofSp3-dependentBNIP3expression.Sp3mightbethemajortranscriptionalregulatorofBNIP3inprostatecanceranditisworthytofurtherstudy.TheregulationofBNIP3bySp3maybeanewcancer-specifictherapeutictargetinprostatecancer.Prostate75:1556–1567,2015.©2015WileyPeriodicals,Inc.NEP表达在常氧和低氧条件下培养的前列腺癌细胞株相比。NEP活性，蛋白水平和mRNA水平均采用酶法测定，Western印迹法和荧光定量PCR分析，分别。电泳迁移率变动分析和染色质免疫沉淀技术（芯片）是用来确认NEP的负调控在转录水平的缺氧反应元件（重点）。进行测试和HIF-1α的相互作用细胞共定位和免疫共沉淀。PC3细胞稳定细胞基因稳定表达的细胞PC3细胞，随着他们的控制，利用慢病毒表达系统的建立。进行测试的细胞HIF-1α蛋白及其下游基因转录的影响进行Westernblot及实时定量PCR。研究缺氧对细胞的潜在作用，细胞生长和克隆形成试验进行稳定表达株PC3细胞进行19、ExpressionofBNIP3correlateswithhypoxia-induciblefactor(HIF)-1alpha,HIF-2alphaandtheandrogenreceptorinprostatecancerandisregulateddirectlybyhypoxiabutnotandrogensincelllines.BNIP3表达与缺氧诱导因子（HIF）-1的相关性，会和雄激素受体在前列腺癌中，受缺氧直接但没有雄激素的细胞系。ShaidaN1,LaunchburyR1,BoddyJL1,JonesC1,CampoL1,TurleyH1,KangaS1,BanhamAH1,MalonePR1,HarrisAL1,FoxSB1[更多]相关基因：BNIP3;HIF1APMID:18163427影响因子3.565BACKGROUND:BNIP3isahypoxia-inducedproteininvolvedincelldeathandsurvivalbutitsroleinhumantumorsisunclear.ThisstudyinvestigatedtheroleofBNIP3inprostatecancer.METHODS:TheexpressionofBNIP3,theandrogenreceptor(AR),hypoxiainduciblefactor(HIF)-1alpha,HIF-2alphaandthehypoxiaregulatedgeneGLUT1wereassessedintissuemicroarraysconstructedfrom149radicalprostatectomyspecimens.Statisticscomparedexpressionofthesefactorsbetweeneachother,conventionalclinicopathologicalparametersandPSArecurrence.SinceanassociationbetweenBNIP3andARandtheHIFswasobserved,theinfluenceofhypoxia,dihydrotestosteroneandtheARblocker,Casodex,wasalsoinvestigatedinprostatecelllines.RESULTS:BNIP3wasexpressedinthenucleusandcytoplasm.Eightof149(5.5%)tumorsshowednoexpression,44/149(29.5%)casesshowedexclusivelycytoplasmicexpression,17/149(11.5%)casesshowedexclusivelynuclearexpressionand80/149(53.5%)casesshowedbothcytoplasmicandnuclearexpression.TherewasasignificantcorrelationbetweencytoplasmicBNIP3expressionandGleasonscore(P=0.005),age(P=0.02),AR(P=0.001),andGLUT1(P=0.006).TherewasasignificantcorrelationbetweennuclearBNIP3expressionandHIF-1alphaexpression(P=0.006)andHIF-2alphaexpression(P=0.013)butnocorrelationbetweenBNIP3andpre-operativePSA,tumorvolume,marginpositivityorcapsularinvasion(allP0.05).TherewasanincreaseinBNIP3expressionunderconditionsofhypoxia(0.1%0(2))butnotwithdihydrotestosteronestimulationorwithCasodextreatment.CONCLUSIONS:ThesefindingssuggestthatBNIP3isdirectlyregulatedbyhypoxiabutthattheremaybeahormonalindependentmechanismcoordinatingtheexpressionofBNIP3inprostatetumors.背景：缺氧诱导BNIP3蛋白参与细胞死亡和生存，但其在人类肿瘤中的作用尚不清楚。这项研究调查了前列腺癌中BNIP3的作用。方法：BNIP3的表达，雄激素受体（AR）、缺氧诱导因子（HIF）-1，HIF-2α的调节在149的前列腺癌根治术标本构建组织芯片进行基因GLUT1的缺氧。统计分析比较了这些因子在各因子之间、常规临床病理参数和抗原特异性复发率之间的比较。自从BNIP3和AR和HIF观察之间的关联，缺氧的影响，睾酮和AR拮抗剂，其中，也在前列腺癌细胞株的研究结果：BNIP3在细胞核和细胞质中表达。149，八（5.5%）肿瘤无表达，44/149（29.5%）的情况下，表现出专门的细胞质表达，17/149（11.5%）的情况下，完全核表达和80/149（53.5%）的情况下，表现出细胞质和核表达。有一个显着的相关性质BNIP3的表达与格里森评分（P=0.005），年龄（P=0.02），AR（P=0.001），和GLUT1（P=0.006）。有一个显着的相关性核BNIP3的表达和HIF-1α的表达（P=0.006）和HIF-2α的表达（P=0.013）无相关性，术前PSABNIP3，与肿瘤体积、边缘阳性或包膜浸润（P0.05）。有一个增加BNIP3的表达在缺氧的条件下（0.1%，0（2））但不与双氢睾酮刺激或比卡鲁胺治疗结论：这些结果表明，BNIP3的缺氧还可能是一种激素自主协调机制在前列腺肿瘤的直接调控BNIP3的表达。22、论文题目：HIF-1α／BNIP3信号通路调节的低氧诱