Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, No. 87 Ding jia qiao Road, Gulou District, Nanjing, 210009, China.
Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, No. 87 Ding jia qiao Road, Gulou District, Nanjing, 210009, China.
Chem Biol Interact. 2023 Mar 1;373:110376. doi: 10.1016/j.cbi.2023.110376. Epub 2023 Feb 1.
A wide variety of chemicals are ubiquitous in the environment and thus exposure to these environmental chemicals poses a serious threat to public health. Particularly, environmental factors such as air pollution, heavy metals, and endocrine-disrupting chemicals (EDCs) can lead to diseases in various organ systems. Recent research in environmental epigenetics has demonstrated that N6-methyladenosine (m6A) modification is a key mechanism of environment-related diseases. m6A modification is the most abundant chemical modification in mRNAs, which can specifically regulate gene expression by affecting RNA translation, stability, processing, and nuclear export. In this review, we discussed how environmental chemicals affected m6A modification and mediated environment-related disease occurrence by classifying the diseases of various systems. Here, we conclude that environmental chemicals alter the levels of m6A and its modulators, which then participate in the occurrence of diseases in various systems by regulating gene expression and downstream signaling pathways such as METTL3/m6A ZBTB4/YTHDF2/EZH2, Foxo3a/FTO/m6A ephrin-B2/YTHDF2, and HIF1A/METTL3/m6A BIRC5/IGF2BP3/VEGFA. Considering the significant role of m6A and its modulators in response to environmental chemicals, they are expected to be used as biomarkers of environment-related diseases. Additionally, targeting m6A modulators using small molecule inhibitors and activators is expected to be a new method for the treatment of environment-related diseases. This review systematically and comprehensively clarifies the important role of m6A in diseases caused by environmental chemicals, thus establishing a scientific basis for the treatment of diseases in various organ systems.
环境中存在着各种各样的化学物质，因此这些环境化学物质的暴露对公众健康构成了严重威胁。特别是，环境污染因素如空气污染、重金属和内分泌干扰化学物质（EDCs）可能导致各种器官系统的疾病。最近的环境表观遗传学研究表明，N6-甲基腺苷（m6A）修饰是与环境相关疾病的关键机制。m6A 修饰是 mRNA 中最丰富的化学修饰，通过影响 RNA 翻译、稳定性、加工和核输出，可特异性调节基因表达。在这篇综述中，我们通过对各种系统疾病的分类，讨论了环境化学物质如何影响 m6A 修饰并介导与环境相关的疾病发生。在这里，我们得出结论，环境化学物质改变了 m6A 及其调节剂的水平，然后通过调节基因表达和下游信号通路（如 METTL3/m6A ZBTB4/YTHDF2/EZH2、Foxo3a/FTO/m6A ephrin-B2/YTHDF2 和 HIF1A/METTL3/m6A BIRC5/IGF2BP3/VEGFA）参与各种系统疾病的发生。鉴于 m6A 及其调节剂在应对环境化学物质中的重要作用，它们有望被用作与环境相关疾病的生物标志物。此外，使用小分子抑制剂和激活剂靶向 m6A 调节剂有望成为治疗与环境相关疾病的新方法。本综述系统全面地阐明了 m6A 在环境化学物质引起的疾病中的重要作用，从而为治疗各种器官系统疾病奠定了科学基础。
