胃癌细胞株中NPRA基因启动子区CpG岛的甲基化分析

目的NPRA-cGMP信号通路系统可激活cGMP依赖的蛋白激酶,活化的蛋白激酶调控离子转运蛋白和转录因子的表达,从而最终影响细胞生长、凋亡、增殖和炎症反应。本研究旨在研究NPRA基因在胃癌细胞中的甲基化状态及其对下游mRNA表达的影响。方法应用亚硫酸氢钠处理基因组DNA后PCR并测序,我们分析了6株胃癌细胞株NPRA基因的甲基化状态及去甲基化试剂对下游mRNA表达的影响。结果在胃癌细胞中发现NPRA基因启动子区存在甲基化畸变并导致下游mRNA表达减少或沉默。去甲基化试剂可逆转mRNA表达沉默。结论胃癌细胞中存在NPRA基因甲基化畸变。

Methylation status in the NPRA promoter in gastric cancer cell lines

Objective NPRA is ANP binding protein that catalyze the synthesis of the intracellular second messenger cGMP.Research suggests that ANP have useful anticancer properties and part of their mechanism of action appears to be mediated by cGMP.It remains to clarify the role of NPRA to mediate ANP effect.In this study,we analyzed NPRA epigenetic inactivation,biological effects,and prognostic significance in gastric cancer.Methods Methylation status was evaluated by bisulfite sequencing.We have identified hypermethylation in the promoter region of NPRA in six gastric cancer cell lines,HGC-27,MGC80-3,NCIN87,AGS,BGC-823,SGC-7901.Results NPRA was silenced or down-regulated in all of six gastric cancer cell lines.Expression levels were restored by exposure to demethylating agents.Conclusion Methylation of the NPRA is frequent in gastric cancer.