Vlahopoulos Spiros, Pan Lang, Varisli Lokman, Dancik Garrett M, Karantanos Theodoros, Boldogh Istvan
First Department of Pediatrics, National and Kapodistrian University of Athens, Thivon & Levadeias 8, Goudi, 11527 Athens, Greece.
Department of Microbiology and Immunology, School of Medicine, University of Texas Medical Branch at Galveston, 301 University Blvd., Galveston, TX 77555, USA.
Cancers (Basel). 2023 Dec 28;16(1):148. doi: 10.3390/cancers16010148.
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.
8-氧代鸟嘌呤糖基化酶1（OGG1）最初被鉴定为催化DNA碱基切除修复途径第一步的酶，现在也被认为是基因表达的调节剂。对癌症而言重要的是，OGG1作为NFκB驱动的基因表达的调节剂发挥作用。具体而言，细胞内的氧化应激会暂时停止与底物结合的OGG1的酶活性。停滞的OGG1促进转录激活因子（如NFκB）与它们的同源位点的DNA结合能力，使得细胞因子和趋化因子得以表达，随后招募炎症细胞。最近，我们强调了OGG1参与基因表达调控的主要方面，这在肺癌发展中具有重要意义。然而，OGG1也与急性髓系白血病的分子基础有关。本综述分析并讨论了这些细胞如何通过氧化还原调节的复杂联系进行适应，即通过OGG1与NFκB的相互作用，这为恶性细胞提供了改变其微环境的替代分子途径，从而实现调节、促进细胞增殖、转移以及逃避治疗药物的杀伤。
