French Samuel W
Department of Pathology, Harbor UCLA Medical Center, Torrance, California, USA.
Alcohol Res. 2013;35(1):57-67.
Epigenetic mechanisms play an extensive role in the development of liver cancer (i.e., hepatocellular carcinoma [HCC]) associated with alcoholic liver disease (ALD) as well as in liver disease associated with other conditions. For example, epigenetic mechanisms, such as changes in the methylation and/or acetylation pattern of certain DNA regions or of the histone proteins around which the DNA is wrapped, contribute to the reversion of normal liver cells into progenitor and stem cells that can develop into HCC. Chronic exposure to beverage alcohol (i.e., ethanol) can induce all of these epigenetic changes. Thus, ethanol metabolism results in the formation of compounds that can cause changes in DNA methylation and interfere with other components of the normal processes regulating DNA methylation. Alcohol exposure also can alter histone acetylation/deacetylation and methylation patterns through a variety of mechanisms and signaling pathways. Alcohol also acts indirectly on another molecule called toll-like receptor 4 (TLR4) that is a key component in a crucial regulatory pathway in the cells and whose dysregulation is involved in the development of HCC. Finally, alcohol use regulates an epigenetic mechanism involving small molecules called miRNAs that control transcriptional events and the expression of genes important to ALD.
表观遗传机制在与酒精性肝病（ALD）相关的肝癌（即肝细胞癌 [HCC]）的发展以及与其他病症相关的肝病中发挥着广泛作用。例如，表观遗传机制，如某些DNA区域或包裹DNA的组蛋白的甲基化和/或乙酰化模式的变化，有助于正常肝细胞逆转为可发展成HCC的祖细胞和干细胞。长期接触饮用酒精（即乙醇）可诱导所有这些表观遗传变化。因此，乙醇代谢会导致形成可引起DNA甲基化变化并干扰调节DNA甲基化正常过程的其他成分的化合物。酒精暴露还可通过多种机制和信号通路改变组蛋白的乙酰化/去乙酰化和甲基化模式。酒精还间接作用于另一种称为Toll样受体4（TLR4）的分子，它是细胞中关键调节途径的关键成分，其失调与HCC的发展有关。最后，饮酒调节一种涉及称为miRNA的小分子的表观遗传机制，这些小分子控制转录事件以及对ALD重要的基因的表达。
