Epigenetic silencing of WIF-1 in hepatocellular carcinomas
Epigenetic silencing of WIF-1 in hepatocellular carcinomas
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DOI：
10.1007/s00432-010-0763-5
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发表时间：
2010-08-01
影响因子：
3.6
通讯作者：
Qin, Wenxin
中科院分区：
文献类型：
--
作者：
Deng, Yun;Yu, Bin;Qin, Wenxin
目的探讨WIF-1基因在肝细胞癌（HCC）中的表达及启动子区甲基化状态，探讨WIF-1基因表达与HCC启动子区甲基化状态的关系。甲基化特异性PCR和亚硫酸氢盐DNA测序用于甲基化分析。结果实时荧光定量PCR分析显示，WIF-1 mRNA在肝癌组织中广泛低表达，且这种低表达依赖于其启动子区域的甲基化程度。结论WIF-1基因启动子区甲基化导致的WIF-1基因沉默可能是HCC中的一个常见事件。
Purpose To examine the expression profile and promoter methylation status of WIF-1 in hepatocellular carcinoma (HCC) and identify the possible relationship between the WIF-1 expression pattern and promoter methylation status.Methods Quantitative real-time PCR was performed to detect mRNA level of WIF-1 in 4 HCC cell lines, 15 paired HCC clinical samples and 3 normal liver tissues. Methylation-speciWc PCR and bisulfite DNA sequencing were used in methylation analysis. In vitro assays for HCC cells, colony formation and cell proliferation assay were carried out to observe the effect of WIF-1 on cell growth; TOP-Xash luciferase analysis was employed to determine its role in the Wnt pathway.Results Quantitative real-time PCR analysis showed the extensive low expression of WIF-1 mRNA in HCC, and this down-regulation was generally dependent on the degree of methylation at its promoter region. In vitro assays indicated WIF-1 can inhibit cell growth by blocking Wnt signaling in HCC cells.Conclusions WIF-1 silencing as a result of its promoter hypermethylation may be a frequent event in HCC.