文章：

OGG1作为表观遗传阅读器影响NFκB：对癌症的启示

OGG1 as an Epigenetic Reader Affects NFκB: What This Means for Cancer

原文发布日期：28 December 2023

DOI: 10.3390/cancers16010148

类型: Article

开放获取: 是

英文摘要：

8-oxoguanine glycosylase 1 (OGG1), which was initially identified as the enzyme that catalyzes the first step in the DNA base excision repair pathway, is now also recognized as a modulator of gene expression. What is important for cancer is that OGG1 acts as a modulator of NFκB-driven gene expression. Specifically, oxidant stress in the cell transiently halts enzymatic activity of substrate-bound OGG1. The stalled OGG1 facilitates DNA binding of transactivators, such as NFκB to their cognate sites, enabling the expression of cytokines and chemokines, with ensuing recruitment of inflammatory cells. Recently, we highlighted chief aspects of OGG1 involvement in regulation of gene expression, which hold significance in lung cancer development. However, OGG1 has also been implicated in the molecular underpinning of acute myeloid leukemia. This review analyzes and discusses how these cells adapt through redox-modulated intricate connections, via interaction of OGG1 with NFκB, which provides malignant cells with alternative molecular pathways to transform their microenvironment, enabling adjustment, promoting cell proliferation, metastasis, and evading killing by therapeutic agents.

摘要翻译： 

8-氧鸟嘌呤DNA糖基化酶1（OGG1）最初被鉴定为催化DNA碱基切除修复途径第一步的酶，现已被确认为基因表达的调节因子。在癌症研究中具有重要意义的是，OGG1作为NFκB驱动基因表达的调节器发挥作用。具体而言，细胞内的氧化应激会暂时抑制底物结合型OGG1的酶活性。这种停滞状态的OGG1促进NFκB等转录激活因子与其同源位点的DNA结合，从而启动细胞因子和趋化因子的表达，进而募集炎症细胞。近期我们重点阐述了OGG1参与基因表达调控的核心机制，这些机制在肺癌发展中具有重要意义。此外，OGG1也被证实与急性髓系白血病的分子基础密切相关。本综述通过分析OGG1与NFκB的相互作用，探讨恶性细胞如何通过氧化还原调控的复杂网络实现适应性改变，这种相互作用为恶性细胞提供了转化微环境的替代分子途径，使其能够适应环境、促进细胞增殖与转移，并逃避治疗药物的杀伤作用。

原文链接：

OGG1 as an Epigenetic Reader Affects NFκB: What This Means for Cancer