简介:Objective:Polycystickidneydisease(PKD)isthemajorcauseofkidneyfailureandmortalityinhumans.Ithasalwaysbeensuspectedthatthedevelopmentofcystickidneydiseasesharesfeatureswithtumorigenesis,althoughtheevidenceisunclear.Methods:Wecrossedp53mutantmice(p53N236S,p53S)withWernersyndromemiceandanalyzedthepathologicalphenotypes.TheRNA-seq,ssGSEAanalysis,andreal-timePCRwereperformedtodissectthegenesignaturesinvolvedinthedevelopmentofdiseasephenotypes.Results:Wefoundenlargedkidneyswithfluid-filledcystsinoffspringmicewithagenotypeofG3mTerc-/-WRN-/-p53S/S(G3TM).PathologyanalysisconfirmedtheoccurrenceofPKD,anditwashighlycorrelatedwiththeincidenceoftumorigenesis.RNA-seqdatarevealedthegenesignaturesinvolvedinPKDdevelopment,anddemonstratedthatPKDandtumorigenesissharedcommonpathways,includingcomplementpathways,lipidmetabolism,mitochondriaenergyhomeostasisandothers.Interestingly,thisG3TMPKDandtheclassicalPKD1/2deficientPKDsharedcommonpathways,possiblybecausethemutantp53ScouldregulatetheexpressionlevelsofPKD1/2,Pkhd1,andHnf1b.Conclusions:WeestablishedadualmousemodelforPKDandtumorigenesisderivedfromabnormalcellularproliferationandtelomeredysfunction.TheinnovativepointofourstudyistoreportPKDoccurringinconjunctionwithtumorigenesis.ThegenesignaturesrevealedmightshednewlightonthepathogenesisofPKD,andprovidenewmolecularbiomarkersforclinicaldiagnosisandprognosis.
简介:目的研究C02对宫颈癌Hela细胞株CDK9基因表达的影响,分析其在癌细胞生长与转移中的作用。方法将宫颈癌Hela细胞株随机分为3组:A组Hela细胞株在压力为8mmHg的纯C02下通气4h,培养24h;B组Hela细胞株在压力为8mmHg的纯C02下通气4h,培养120h;C组Hela细胞株未进行C02处理,细胞株置于常规细胞培养箱中培养120h。采用RT-PCR法检测A、B、C组宫颈癌Hela细胞CDK9mRNA的表达。结果A、B组与C组比较,A、B组CDK9mRNA的相对表达量明显下调(P〈0.05);B组与A组比较,B组CDK9mRNA的相对表达量比A组下调更显著(P〈0.01)。结论宫颈癌Hela细胞CDK9基因在C02作用下受抑制出现表达下调,且随C02作用时间越长,CDK9基因相对表达量降低越明显。