维生素C:表观遗传调节剂

F. Pehlivan
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引用次数: 6

摘要

维生素C是人体必需的微量营养素,是自由基清除剂;同时具有阻断致癌物诱导的致癌转化等功能。关于维生素C在癌症中的潜在作用的另一种观点来自于它对激活参与DNA和组蛋白去甲基化的10 - 11易位(TET)酶的重要性的发现。异常的DNA和组蛋白甲基化是所有癌症的标志,可能是编码这些调节酶的基因表达改变或点突变的结果。最近的研究表明,维生素C增强了DNA甲基转移酶抑制剂的作用。表观遗传改变和基因突变是导致癌症发生的原因。维生素C作为TET双加氧酶的辅助因子调节DNA去甲基化,是基因组与环境界面的关键介质。研究表明,维生素C通过增强TET酶来促进DNA甲基化的活性去除,这有助于消除DNA甲基化和由其编码的表观遗传记忆,从而改善分化细胞的重编程,使其进入胚胎样状态。本文综述了维生素C在表观遗传调控中的重要作用及其在癌症患者表观遗传治疗中的潜力。
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Vitamin C: An Epigenetic Regulator
Vitamin C is an essential micronutrient, a free radical scavenger; while it has functions such as blocking oncogenic transformation induced by carcinogens. A different view of the potential action of vitamin C in cancer came from the discovery of its importance for activation of ten-eleven translocation (TET) enzymes that are involved in demethylation of DNA and histones. Aberrant DNA and histone methylation are hallmarks of all cancers and may result from altered expression or point mutations in the genes encoding these regulatory enzymes. Recent studies have shown that vitamin C potentiates the effects of DNA methyltransferase inhibi-tors. Epigenetic alterations, along with genetic mutations, are known to contribute to onset of cancer. Vitamin C is found to be a key mediator of the interface between genome and environment, regulating DNA demethylation as a cofactor for TET dioxygenases. It is shown that vitamin C drives active removal of DNA methylation by enhancing TET enzymes, which helps to erase DNA methylation and epigenetic memory encoded by it to improve reprogramming of differentiated cells to an embryonic-like state. Here, an overview of the role of vitamin C as an essential factor for epigenetic regulation and its potential in epigenetic therapy in cancer patients is provided.
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