ROS-Mediated DNA Methylation Pattern Alterations in Carcinogenesis
ROS-Mediated DNA Methylation Pattern Alterations in Carcinogenesis
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DOI：
10.2174/1389450116666150113121054
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发表时间：
2015-01-01
影响因子：
3.2
通讯作者：
Ni, Xiaohua
中科院分区：
文献类型：
--
作者：
Wu, Qihan;Ni, Xiaohua
活性氧（ROS）和DNA甲基化水平升高是各种类型癌细胞的特征。然而，这两者之间的关系并没有得到很好的理解。在这里，我们将讨论ROS和DNA甲基化之间的因果关系。癌症研究表明，DNA甲基化的失调导致区域性CpG岛高甲基化和普遍的基因组低甲基化。ROS诱导的氧化应激与肿瘤抑制基因（TSG）启动子区域的异常高甲基化和整体低甲基化相关。DNA氧化结构8-羟基-2 '-脱氧鸟苷（8-OHdG）可通过抑制附近胞嘧啶碱基的DNA甲基化来诱导DNA低甲基化，而另一种DNA氧化结构5-羟甲基胞嘧啶（5 hmC）可实现主动的DNA去甲基化过程，从而导致DNA低甲基化。近年来，研究发现活性氧可以作为DNA甲基化的催化剂，进一步解释了TSG启动子的高甲基化。此外，ROS可以通过上调DNA甲基转移酶（DNMT）的表达或形成新的含有DNMT的复合物来诱导位点特异性的超甲基化。此外，这些ROS诱导的DNA甲基化模式改变不仅与恶性转化有关，而且与许多肿瘤的进展有关。综上所述，ROS通过不同的机制影响DNA甲基化的两个方面，在肿瘤细胞的表观遗传调控中发挥重要作用。因此，理解导致与ROS相关的表观遗传修饰的机制可能有助于更好地理解癌症的发生和进展，并有助于开发潜在的生物标志物，以更好地诊断癌症和制定新的治疗策略。
Elevated levels of both reactive oxygen species (ROS) and DNA methylation are characteristic of various types of cancer cells. However, the relation between these two is not well understood. Here we will discuss the cause-consequence relationship between ROS and DNA methylation. Cancer research reveals that disregulation of DNA methylation results in regional CpG island hypermethylation and generalized genomic hypomethylation. ROS-induced oxidative stress is associated with both aberrant hypermethylation of tumor suppressor gene (TSG) promoter regions and global hypomethylation. The DNA oxidation structure, 8-hydroxy-2'-deoxyguanosine (8-OHdG), can induce DNA hypomethylation by inhibiting DNA methylation at nearby cytosine bases, while another DNA oxidation structure, 5-hydroxymethylcytosine (5hmC), may achieve active DNA demethylation processes, thus, causing DNA hypomethylation. Recently, it has been found that ROS can function as catalysts of DNA methylation, further accounting for TSG promoter hypermethylation. Moreover, ROS may induce site-specific hypermethylation via either the up-regulation of expression of DNA methyltransferases (DNMTs) or the formation of a new DNMT containing complex. In addition, these ROS-induced DNA methylation pattern alterations have been implicated with not only malignant transformation, but also the progression of numerous tumors. In conclusion, ROS can influence both aspects of DNA methylation changes through different mechanisms, which play an important role of epigenetic regulation in cancer cells. Therefore, the comprehension of mechanisms leading to epigenetic modifications associated with ROS may help better understand the carcinogenesis and progression, as well as aid in the development of potential biomarkers for better cancer diagnostics and novel therapeutic strategies.