摘要
AIMToinvestigatetherolesandinteractionsofmutThomolog（MTH）-1andhypoxia-induciblefactor（HIF）-1αinhumancolorectalcancer（CRC）.METHODS：TheexpressionanddistributionofHIF-1αandMTH-1proteinsweredetectedinhumanCRCtissuesbyimmunohistochemistryandquantitativerealtimepolymerasechainreaction（qRT-PCR）.SW480andHT-29cellswereexposedtonormoxiaorhypoxia.ProteinandmRNAlevelsofHIF-1αandMTH-1wereanalyzedbywesternblottingandqRT-PCR,respectively.InordertodeterminetheeffectofHIF-1αontheexpressionofMTH-1andtheamountof8-oxodeoxyguanosinetriphosphate（dGTP）inSW480andHT-29cells,HIF-1αwassilencedwithsmallinterferingRNA（siRNA）.GrowthstudieswereconductedoncellswithHIF-1αinhibitionusingaxenografttumormodel.Finally,MTH-1proteinwasdetectedbywesternblottinginvivo.RESULTS：HighMTH-1mRNAexpressionwasdetectedin64.2%ofcases（54/84）,andthiswassignificantlycorrelatedwithtumorstage（P=0.023）andsize（P=0.043）.HIF-1αproteinexpressionwascorrelatedsignificantlywithMTH-1expression（R=0.640;P〈0.01）inhumanCRCtissues.HypoxicstressinducedmRNAandproteinexpressionofMTH-1inSW480andHT-29cells.InhibitionofHIF-1αbysiRNAdecreasedtheexpressionofMTH-1andledtotheaccumulationof8-oxo-dGTPinSW480andHT-29cells.Intheinvivoxenografttumormodel,expressionofMTH-1wasdecreasedintheHIF-1αsiRNAgroup,andthetumorvolumewasmuchsmallerthanthatinthemocksiRNAgroup.CONCLUSION：MTH-1expressioninCRCcellswasupregulatedviaHIF-1αinresponsetohypoxicstress,emphasizingthecrucialroleofHIF-1α-inducedMTH-1intumorgrowth.
出版日期
2015年12月22日（中国期刊网平台首次上网日期，不代表论文的发表时间）
