Sonic hedgehog在大肠癌细胞株中表达缺失与其启动子高甲基化有关

Loss of Sonic hedgehog expression in colorectal cancer cell lines is associated with hypermethylation of its promoter

目的:研究sonic hedgehog(SHH)在大肠癌细胞株的表达及其调控机制。方法:RT-PCR检测SHH mRNA在大肠癌细胞株HCT-8、SW1116、SW480及LOVO中的表达,去甲基化试验观察5-氮-2-脱氧胞苷(5-aza-2′-deoxycytidine)处理细胞株后对SHH mRNA表达的影响,采用亚硫酸盐修饰后测序法检测SHH启动子区甲基化状况。结果:SHH mRNA在HCT-8中仅有弱表达,在SW1116、SW480及LOVO中表达缺失,去甲基化处理后,其表达与对照组相比显著增强(P<0.001);SHH启动子在大肠癌细胞株中为高甲基化状态。结论:SHH在大肠癌细胞株中表达缺失与其启动子高甲基化有关。

Objective： To investigate the expression of Sonic hedgehog（SHH） in colorectal cancer cell lines and its regulation mechanism.Methods： SHH mRNA expression in 4 colorectal cancer cell lines was examined by RT-PCR,and then determined after demethylation treatment with 5-aza-2′-deoxycytidine.The methylation status of SHH promoter in colorectal cancer cells was detected by bisulfite sequencing.Results： SHH mRNA was expressed weakly in HCT-8 cell,and lost in SW1116,SW480 and LOVO cells.After demethylation treatment,expression of SHH mRNA increased significantly（P 0.001）.SHH promoter was hypermethylated in colorectal cancer lines.Conclusion：Loss of SHH expression in colorectal cancer cell lines is associated with hypermethylation of its promoter.