Oxidative stress: One potential factor for arsenite-induced increase of N-methyladenosine in human keratinocytes.

N-methyladenosine (mA) modification is affected by oxidative stress and gets involved in arsenite toxicity. However, whether oxidative stress is one factor in arsenite-induced alteration of mA levels remains unclear. Here, reactive oxygen species (ROS), product of lipid peroxidation (MDA), antioxidants (GSH and SOD), mA levels, mA methyltransferases (METTL3, METTL14, and WTAP) and demethylases (FTO and ALKBH5) were detected in human keratinocytes exposed to different concentrations of arsenite. Antioxidant N-acetylcysteine was used to assess the influence of arsenite-induced oxidative stress on mA modification. Possible regulations of mA modification induced by arsenite were explored using bioinformatic analysis. Our results demonstrated that arsenite-induced oxidative stress increased the levels of mA methylation possibly by mediating mA methyltransferases and demethylases, especially elevated expressions of WTAP and METTL14, in human keratinocytes. Whereas N-acetylcysteine suppressed the elevated mA level and its methyltransferases in human keratinocytes exposed to arsenite. Furthermore, arsenite-induced oxidative stress might mediate mA methyltransferases and demethylases by reducing transcription of 4 genes (HECTD4, ABCA5, SLC22 A17 and KCNQ5) according to our bioinformatic analysis and experiments. Additionally, GO and Pathway analysis further suggested that the increase of mA modification in arsenite-induced oxidative stress might be involved in some biological processes such as positive regulation of GTPase activity, apoptotic process, and platelet activation. Taken together, our study revealed the significant role of oxidative stress in mA modification induced by arsenite.