The Role of 8-oxoG Repair Systems in Tumorigenesis and Cancer Therapy.
The Role of 8-oxoG Repair Systems in Tumorigenesis and Cancer Therapy.
复制标题
8-oxoG 修复系统在肿瘤发生和癌症治疗中的作用
作者：
肿瘤发生与突变的积累高度相关。丰富和广泛的DNA氧化产物8-氧代鸟嘌呤（8-oxoG），如果不被8-oxoG修复系统修复，可能会导致突变。因此，8-oxoG的积累在肿瘤发生中起着至关重要的作用。为了避免8-oxoG在基因组中的积累，由8-氧代鸟嘌呤DNA糖基化酶1（OGG 1）启动的碱基切除修复（BER）负责去除基因组8-oxoG。已经证明，与正常组织细胞相比，癌细胞中的8-oxoG水平显著升高，并且一些抗肿瘤药物诱导的DNA损伤涉及直接或间接干扰BER，特别是通过诱导活性氧（ROS）的产生和积累，这可导致肿瘤细胞死亡。此外，BER核心成分的缺失可导致小鼠胚胎或出生后早期致死。因此，用抑制剂靶向8-oxoG修复系统是肿瘤治疗的一种有前途的途径。在这项研究中，我们总结了8-oxoG积累对肿瘤发生的影响，以及利用8-oxoG修复酶靶向的癌症治疗方法的现状，以及涉及外源性ROS诱导剂的可能的协同致死策略。
Tumorigenesis is highly correlated with the accumulation of mutations. The abundant and extensive DNA oxidation product, 8-Oxoguanine (8-oxoG), can cause mutations if it is not repaired by 8-oxoG repair systems. Therefore, the accumulation of 8-oxoG plays an essential role in tumorigenesis. To avoid the accumulation of 8-oxoG in the genome, base excision repair (BER), initiated by 8-oxoguanine DNA glycosylase1 (OGG1), is responsible for the removal of genomic 8-oxoG. It has been proven that 8-oxoG levels are significantly elevated in cancer cells compared with cells of normal tissues, and the induction of DNA damage by some antitumor drugs involves direct or indirect interference with BER, especially through inducing the production and accumulation of reactive oxygen species (ROS), which can lead to tumor cell death. In addition, the absence of the core components of BER can result in embryonic or early post-natal lethality in mice. Therefore, targeting 8-oxoG repair systems with inhibitors is a promising avenue for tumor therapy. In this study, we summarize the impact of 8-oxoG accumulation on tumorigenesis and the current status of cancer therapy approaches exploiting 8-oxoG repair enzyme targeting, as well as possible synergistic lethality strategies involving exogenous ROS-inducing agents.
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影响因子：
11.4
作者：
Chao MR;Evans MD;Hu CW;Ji Y;Møller P;Rossner P;Cooke MS
通讯作者：
Cooke MS
影响因子：
3.7
作者：
Duan WX;Hua RX;Yi W;Shen LJ;Jin ZX;Zhao YH;Yi DH;Chen WS;Yu SQ
通讯作者：
Yu SQ
DOI：
10.1016/j.mrfmmm.2014.11.010
发表时间：
2015-06-01
影响因子：
2.3
作者：
Coppede, Fabio;Migliore, Lucia
通讯作者：
Migliore, Lucia
影响因子：
6.1
作者：
Ventura I;Russo MT;De Nuccio C;De Luca G;Degan P;Bernardo A;Visentin S;Minghetti L;Bignami M
通讯作者：
Bignami M
DOI：
10.1038/nrm.2017.53
发表时间：
2017-10
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Ray Chaudhuri A;Nussenzweig A
通讯作者：
Nussenzweig A