The emerging role of N6-methyladenine RNA methylation in metal ion metabolism and metal-induced carcinogenesis

Abstract

N⁶-methyladenine (m⁶A) is the most common and abundant internal modification in eukaryotic mRNAs, which can regulate gene expression and perform important biological tasks. Metal ions participate in nucleotide biosynthesis and repair, signal transduction, energy generation, immune defense, and other important metabolic processes. However, long-term environmental and occupational exposure to metals through food, air, soil, water, and industry can result in toxicity, serious health problems, and cancer. Recent evidence indicates dynamic and reversible m⁶A modification modulates various metal ion metabolism, such as iron absorption, calcium uptake and transport. In turn, environmental heavy metal can alter m⁶A modification by directly affecting catalytic activity and expression level of methyltransferases and demethylases, or through reactive oxygen species, eventually disrupting normal biological function and leading to diseases. Therefore, m⁶A RNA methylation may play a bridging role in heavy metal pollution-induced carcinogenesis. This review discusses interaction among heavy metal, m⁶A, and metal ions metabolism, and their regulatory mechanism, focuses on the role of m⁶A methylation and heavy metal pollution in cancer. Finally, the role of nutritional therapy that targeting m⁶A methylation to prevent metal ion metabolism disorder-induced cancer is summarized.

Keywords: Cancers; Metal ions; N(6)-methyladenine; Nutritional therapy.