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作 者:吕红慧 张美英 郭明洲 LYU Honghui;ZHANG Meiying;GUO Mingzhou(School of Pharmaceutical Sciences,Zhengzhou University,Zhengzhou 450001;Department of Gastroenterology&Hepatology,the First Medical Center,Chinese PLA General Hospital,China)
机构地区:[1]郑州大学药学院,河南郑州450001 [2]中国人民解放军总医院第一医学中心消化内科医学部
出 处:《胃肠病学和肝病学杂志》2021年第7期754-757,762,共5页Chinese Journal of Gastroenterology and Hepatology
基 金:国家重点研发计划(2018YFA0208902,2020YFC2002705);国家自然科学基金委员会资助项目(81672318,U1604281);北京市自然科学基金重点项目(7171008);国家重点科学仪器专项计划(2011YQ03013405)。
摘 要:目的探讨连接粘附分子3(junctional adhesion molecules 3,JAM3)基因启动子区在胰腺癌中的甲基化情况及其表达调控机制。方法应用半定量RT-PCR和甲基化特异性PCR技术对8株胰腺癌细胞系(Panc3.11、Panc1、SW1990、Miapaca2、Aspc1、Panc 5.04、Panc10.05、CFpac1)和79例胰腺癌组织进行分析。结果JAM3基因在Panc1、Miapaca2、Panc5.04、CFpac1细胞系中高表达,这些细胞启动子区为非甲基化状态。JAM3基因在Panc3.11、SW1990、Aspc1、Panc10.05细胞系中表达缺失,其启动子区为完全甲基化状态。去甲基化药物5-aza-dc处理后,缺失表达的细胞系恢复了JAM3的表达。这些结果表明JAM3基因在胰腺癌细胞中的表达受启动子区甲基化调控。JAM3基因在胰腺癌组织中甲基化率为48.1%(38/79),且JAM3甲基化与肿瘤分化相关(P<0.05),JAM3甲基化是胰腺癌诊断的潜在标志物。结论JAM3基因在胰腺癌组织中频繁发生甲基化,且其表达受启动子区甲基化调控。Objective To investigate the methylation status of JAM3 in pancreatic cancer and its expression regulation.Methods 8 pancreatic cancer cell lines(Panc3.11,Panc1,SW1990,Miapaca2,Aspc1,Panc5.04,Panc10.05,CFpac1)and 79 cases of pancreatic cancer samples were employed.Semi-quantitative RT-PCR and methylation specific PCR(MSP)techniques were applied to detect the expression and methylation status of JAM3.Results JAM3 was highly expressed and unmethylated in Panc1,Miapaca2,Panc5.04 and CFpac1 cells.Loss of JAM3 expression and promoter region complete methylation was found in Panc3.11,SW1990,Aspc1 and Panc10.05 cells.Reexpression of JAM3 was induced by 5-Aza-2′deoxycytidine(5-aza-dc)in JAM3 methylated cells.The results suggested that the expression of JAM3 was regulated by promoter region methylation.JAM3 was methylated in 48.1%(38/79)of pancreatic cancer samples,and JAM3 methylation was associated to cancer differentiation significantly(P<0.05).Methylation of JAM3 may serve as a potential diagnostic marker of pancreatic cancer.Conclusion JAM3 gene is frequently methylated in human pancreatic cancer and the expression of JAM3 is regulated by promoter region methylation.
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