目的:探讨启动子区甲基化对肝细胞癌中锌指蛋白331(zinc-finger protein331,ZNF331)表达的调控及意义.方法:采用甲基化特异性PCR(methylation specific PCR,MSP)检测ZNF331在肝癌细胞系和50例原发性肝细胞癌组织中的甲基化状况,并采用...目的:探讨启动子区甲基化对肝细胞癌中锌指蛋白331(zinc-finger protein331,ZNF331)表达的调控及意义.方法:采用甲基化特异性PCR(methylation specific PCR,MSP)检测ZNF331在肝癌细胞系和50例原发性肝细胞癌组织中的甲基化状况,并采用半定量RT-PCR分析5-杂氮-2'-脱氧胞苷(5-Aza-2'-deoxycytidine,5-Aza)处理前后肝癌细胞系中ZNF331的表达情况.结果:ZNF331在肝癌细胞系HBXF344、PLC/PRF/5、HepG2、BEL-7402中低表达,SNU449中表达正常.5-Aza处理后HBXF344、HepG2、BEL-7402及PLC/PRF/5中ZNF331恢复表达.50例原发性肝细胞癌标本中,ZNF331启动子区的甲基化率为80%(40/50),而10例正常肝脏组织中ZNF331均无甲基化.ZNF331启动子区的甲基化与肝细胞癌患者的性别、年龄、肿瘤直径大小、血清甲胎蛋白值、肝炎病毒感染、分化水平及TNM分期均无关联(P>0.05).结论:ZNF331启动子区高甲基化是肝癌的频发事件,ZNF331基因表达受启动子区甲基化调控.展开更多
【目的】探讨乳腺癌易感基因PALB2启动子甲基化与乳腺癌临床病理特征、预后的关系。【方法】采用MSP法检测128例乳腺癌石蜡组织中PALB2启动子甲基化情况，分析其与乳腺癌临床病理特征及临床预后的相关性。【结果】128例乳腺癌中有淋巴...【目的】探讨乳腺癌易感基因PALB2启动子甲基化与乳腺癌临床病理特征、预后的关系。【方法】采用MSP法检测128例乳腺癌石蜡组织中PALB2启动子甲基化情况，分析其与乳腺癌临床病理特征及临床预后的相关性。【结果】128例乳腺癌中有淋巴结转移的患者中14．04％（8／57）检测出PALB2启动子甲基化，高于无淋巴结转移患者的2．82％（2／71），且差异具有显著性（ P ＜0．05）。PALB2启动子甲基化组的中位无瘤生存时间与中位总生存时间分别为50个月和51．5个月，无甲基化组的中位无瘤生存时间与总生存时间分别为54个月和88个月，两者相比较差异均具有显著性（ P ＜0．01）。乳腺癌患者预后相关因素分析提示N分期及PALB2启动子甲基化情况均是影响乳腺癌患者预后的独立危险因素。【结论】乳腺癌组织PALB2基因启动子甲基化情况与是否有淋巴结转移相关。与PALB2启动子无甲基化组比较，有甲基化组乳腺癌患者的预后更差。PALB2启动子甲基化作为影响乳腺癌患者预后的独立危险因素，对于评估患者临床预后有着重要意义。展开更多
Heterochromatic siRNAs regulate transcriptional gene silencing by inducing DNA methylation and histone H3K9 dimethylation.Recent advances have revealed the distinct phases involved in siRNA mediated silencing pathway,...Heterochromatic siRNAs regulate transcriptional gene silencing by inducing DNA methylation and histone H3K9 dimethylation.Recent advances have revealed the distinct phases involved in siRNA mediated silencing pathway,although the precise functions of a number of factors remain undesignated,putative mechanisms for the con-nection between DNA and histone methylation have been investigated,and much effort has been invested to understand the biological functions of siRNA-mediated epigenetic modifi cation.In this review,we summarize the mechanism of siRNA-mediated epigenetic modification,which involves the production of siRNA and the recruit-ments of DNA and histone methytransferases to the target sequences assisted by complementary pairing between 24-nt siRNAs and nascent scaffold RNAs,the roles of siRNA-mediated epigenetic modifi cation in maintaining genome stability and regulating gene expression have been dis-cussed,newly identified players of the siRNA mediated silencing pathway have also been introduced.展开更多
文摘目的:探讨启动子区甲基化对肝细胞癌中锌指蛋白331(zinc-finger protein331,ZNF331)表达的调控及意义.方法:采用甲基化特异性PCR(methylation specific PCR,MSP)检测ZNF331在肝癌细胞系和50例原发性肝细胞癌组织中的甲基化状况,并采用半定量RT-PCR分析5-杂氮-2'-脱氧胞苷(5-Aza-2'-deoxycytidine,5-Aza)处理前后肝癌细胞系中ZNF331的表达情况.结果:ZNF331在肝癌细胞系HBXF344、PLC/PRF/5、HepG2、BEL-7402中低表达,SNU449中表达正常.5-Aza处理后HBXF344、HepG2、BEL-7402及PLC/PRF/5中ZNF331恢复表达.50例原发性肝细胞癌标本中,ZNF331启动子区的甲基化率为80%(40/50),而10例正常肝脏组织中ZNF331均无甲基化.ZNF331启动子区的甲基化与肝细胞癌患者的性别、年龄、肿瘤直径大小、血清甲胎蛋白值、肝炎病毒感染、分化水平及TNM分期均无关联(P>0.05).结论:ZNF331启动子区高甲基化是肝癌的频发事件,ZNF331基因表达受启动子区甲基化调控.
文摘【目的】探讨乳腺癌易感基因PALB2启动子甲基化与乳腺癌临床病理特征、预后的关系。【方法】采用MSP法检测128例乳腺癌石蜡组织中PALB2启动子甲基化情况，分析其与乳腺癌临床病理特征及临床预后的相关性。【结果】128例乳腺癌中有淋巴结转移的患者中14．04％（8／57）检测出PALB2启动子甲基化，高于无淋巴结转移患者的2．82％（2／71），且差异具有显著性（ P ＜0．05）。PALB2启动子甲基化组的中位无瘤生存时间与中位总生存时间分别为50个月和51．5个月，无甲基化组的中位无瘤生存时间与总生存时间分别为54个月和88个月，两者相比较差异均具有显著性（ P ＜0．01）。乳腺癌患者预后相关因素分析提示N分期及PALB2启动子甲基化情况均是影响乳腺癌患者预后的独立危险因素。【结论】乳腺癌组织PALB2基因启动子甲基化情况与是否有淋巴结转移相关。与PALB2启动子无甲基化组比较，有甲基化组乳腺癌患者的预后更差。PALB2启动子甲基化作为影响乳腺癌患者预后的独立危险因素，对于评估患者临床预后有着重要意义。
基金the National Natural Science Foundation of China(Grant No.30970265)to B.X.M.and(Grant No.31210103901)to X.F.C.
文摘Heterochromatic siRNAs regulate transcriptional gene silencing by inducing DNA methylation and histone H3K9 dimethylation.Recent advances have revealed the distinct phases involved in siRNA mediated silencing pathway,although the precise functions of a number of factors remain undesignated,putative mechanisms for the con-nection between DNA and histone methylation have been investigated,and much effort has been invested to understand the biological functions of siRNA-mediated epigenetic modifi cation.In this review,we summarize the mechanism of siRNA-mediated epigenetic modification,which involves the production of siRNA and the recruit-ments of DNA and histone methytransferases to the target sequences assisted by complementary pairing between 24-nt siRNAs and nascent scaffold RNAs,the roles of siRNA-mediated epigenetic modifi cation in maintaining genome stability and regulating gene expression have been dis-cussed,newly identified players of the siRNA mediated silencing pathway have also been introduced.
