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首页> 外文期刊>American Journal of Physiology >Role of promoter methylation in increased methionine adenosyltransferase 2A expression in human liver cancer.
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Role of promoter methylation in increased methionine adenosyltransferase 2A expression in human liver cancer.

机译：启动子甲基化在人肝癌中增加蛋氨酸腺苷转移酶2A表达中的作用。

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摘要

Methionine adenosyltransferase (MAT), an essential enzyme that catalyzes the formation of S-adenosylmethionine (SAM), is encoded by two genes, MAT1A (liver-specific) and MAT2A (non-liver-specific). We showed a switch from MAT1A to MAT2A expression in human liver cancer, which facilitates cancer cell growth. The present work examined the role of methylation in MAT2A transcriptional regulation. We found that the human MAT2A promoter is hypomethylated in hepatocellular carcinoma, in which the gene is upregulated transcriptionally, but hypermethylated in normal liver, in which the gene is minimally expressed. Luciferase activities driven by in vitro methylated MAT2A promoter constructs were 75-95% lower than activities driven by unmethylated constructs. SAM treatment of Hep G2 cells reduced MAT2A endogenous expression by 75%, hypermethylated the MAT2A promoter, and reduced luciferase activities driven by MAT2A promoter constructs by 65-75% while not affecting MAT1A's promoter activity. Treatment of adult rat and human hepatocytes with trichostatin A, an inhibitor of histone deacetylase, upregulated MAT2A expression by more than fourfold. Collectively, these results suggest that MAT2A expression is regulated by promoter methylation and histone acetylation.
机译：甲硫氨酸腺苷基转移酶（MAT）是催化S-腺苷甲硫氨酸（SAM）形成的必需酶，由两个基因MAT1A（肝特异性）和MAT2A（非肝特异性）编码。我们显示人类肝癌中从MAT1A转换为MAT2A表达，这有助于癌细胞的生长。目前的工作审查了甲基化在MAT2A转录调控中的作用。我们发现，人MAT2A启动子在肝细胞癌中是低甲基化的，在该基因中该基因在转录上被上调，而在正常肝中，该基因的最低表达是高甲基化的。由体外甲基化的MAT2A启动子构建体驱动的荧光素酶活性比未甲基化的构建体驱动的活性低75-95％。 SAM处理Hep G2细胞可使MAT2A内源性表达降低75％，使MAT2A启动子超甲基化，并使MAT2A启动子构建体驱动的萤光素酶活性降低65-75％，同时不影响MAT1A的启动子活性。用组蛋白脱乙酰基酶抑制剂曲古抑菌素A处理成年大鼠和人肝细胞，使MAT2A表达上调四倍以上。总的来说，这些结果表明MAT2A表达受启动子甲基化和组蛋白乙酰化的调节。

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