组蛋白修饰和 DNA 甲基化在调控人胃癌细胞 O6-甲基鸟嘌呤-DNA 甲基转移酶基因表达中的作用。
Role of histone modifications and DNA methylation in the regulation of O6-methylguanine-DNA methyltransferase gene expression in human stomach cancer cells.
机构信息
Department of Surgical Oncology, the First Affiliated Hospital, China Medical University, Shenyang, China.
出版信息
Cancer Invest. 2010 May;28(4):331-9. doi: 10.3109/07357900903179633.
To determine a possible function of histone modifications in stomach carcinogenesis, we analyzed global and MGMT-promoter levels of di-methyl-H3-K9, di-methyl-H3-K4 and acetyl-H3-K9, as well as MGMT DNA methylation and mRNA expression following treatment with 5-aza-2' -deoxycytidine and/or Trichostatin A. We found that histone H3-K9 di-methylation, H3-K4 di-methylation, H3-K9 acetylation and DNA methylation work in combination to silence MGMT. The results indicate that histone modifications as well as DNA methylation may be involved in stomach carcinogenesis. In addition to its effect on DNA methylation, 5-aza-2' -deoxycytidine can act at histone modification level to reactivate MGMT expression in a region-specific and DNA methylation-dependent manner.
为了确定组蛋白修饰在胃癌发生中的可能作用，我们分析了经 5-氮杂-2'-脱氧胞苷和/或曲古抑菌素 A 处理后，组蛋白 H3-K9 二甲基化、H3-K4 二甲基化、H3-K9 乙酰化和 MGMT 启动子甲基化以及 mRNA 表达的总体水平和 MGMT 启动子水平。我们发现组蛋白 H3-K9 二甲基化、H3-K4 二甲基化、H3-K9 乙酰化和 DNA 甲基化共同作用沉默 MGMT。结果表明，组蛋白修饰和 DNA 甲基化可能参与胃癌的发生。除了对 DNA 甲基化的影响外，5-氮杂-2'-脱氧胞苷还可以在组蛋白修饰水平上作用，以区域特异性和 DNA 甲基化依赖的方式重新激活 MGMT 的表达。
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