circZNF462 inhibits cadmium-induced DNA damage in bronchial epithelial cells by regulating chromatin accessibility

Abstract Genetic damage is an early effect of altered cell function and tumorigenesis. Analysis of epigenetic alterations in genetic damage in the context of environmental heavy metal-induced cytotoxicity highlights the importance of environment–epigenetics–genetics interactions. The mechanism through which circular RNA (circRNA), an important molecule in epigenetics, regulates cadmium (Cd)-induced DNA damage is unknown. Herein, we report that circRNA circZNF462 regulates chromatin accessibility and inhibits DNA damage after Cd exposure. Downregulation of circZNF462 was associated with DNA damage in a model of 10 μM Cd-exposed bronchial epithelial cells. Chromatin accessibility increased after Cd exposure. Downregulation of circZNF462 significantly increased chromatin accessibility, thereby increasing DNA damage. MCM5 was significantly upregulated after Cd exposure and was negatively correlated with circZNF462. Furthermore, in the Cd exposure model, downregulated circZNF462 increased the levels of MCM5 and facilitated chromatin opening. Reduction of MCM5 reversed the induction of DNA damage after Cd exposure by low levels of circZNF462. These findings underscore the role of circZNF462-regulated chromatin accessibility in Cd-induced DNA damage and suggest that the epigenetic molecule circZNF462 might serve as a potential biomarker and early intervention target for preventing environmentally related genetic damage events.