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氧化应激通过OGG1介导的SP1结合调控肺癌细胞中CDH3的表达。

Oxidative Stress Regulates CDH3 Expression in Lung Cancer Cells via OGG1-Mediated SP1 Binding.

作者信息

Ma Ying, Guo Jiarong, Xu Shichu, Hou Yanjun, Pan Feiyan, Guo Zhigang

机构信息

Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 Wen Yuan Road, Nanjing 210023, China.

出版信息

Antioxidants (Basel). 2025 Mar 11;14(3):332. doi: 10.3390/antiox14030332.

Abstract

Oxidative stress, resulting from an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, plays a crucial role in tumor development. Tumor cells often experience elevated oxidative stress due to rapid proliferation and unstable metabolism, leading to DNA damage. The enzyme 8-oxoguanine DNA glycosidase (OGG1) is central to repairing oxidative DNA damage, thereby maintaining genomic stability. In addition to its DNA repair function, OGG1 also plays a role in gene expression under oxidative stress. This study examined the expression pattern of cadherin-3 (CDH3), a cell adhesion protein associated with cancer metastasis and poor prognosis, under oxidative stress. Our findings showed that oxidative stress upregulated CDH3 expression, with OGG1 playing a pivotal role. Analysis of the promoter revealed SP1 binding sites, and ChIP-qPCR assays confirmed OGG1's involvement in modulating SP1 binding. These results provided new insights into the regulation of CDH3 under oxidative stress and suggested potential therapeutic strategies targeting CDH3 in cancer treatment.

摘要

氧化应激是由活性氧(ROS)生成与抗氧化防御之间的失衡所导致的,在肿瘤发展过程中起着至关重要的作用。由于快速增殖和不稳定的新陈代谢,肿瘤细胞常常经历氧化应激升高的情况,从而导致DNA损伤。8-氧代鸟嘌呤DNA糖苷酶(OGG1)对于修复氧化DNA损伤至关重要,进而维持基因组稳定性。除了其DNA修复功能外,OGG1在氧化应激下的基因表达中也发挥作用。本研究检测了钙黏蛋白-3(CDH3)在氧化应激下的表达模式,CDH3是一种与癌症转移和不良预后相关的细胞黏附蛋白。我们的研究结果表明,氧化应激上调了CDH3的表达,其中OGG1起关键作用。对启动子的分析揭示了SP1结合位点,染色质免疫沉淀定量PCR(ChIP-qPCR)分析证实OGG1参与调节SP1结合。这些结果为氧化应激下CDH3的调控提供了新的见解,并为癌症治疗中针对CDH3的潜在治疗策略提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a5b/11939367/7c0b8ec8c037/antioxidants-14-00332-g001.jpg

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