Interaction between N6-methyladenosine (m6A) modification and environmental chemical-induced diseases in various organ systems

Abstract

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.

Keywords: Environment-related diseases; Environmental chemicals; Regulator mechanism; m6A modification.