Oxygenated Polycyclic aromatic hydrocarbons (Oxy-PAHs) facilitate lung cancer metastasis by epigenetically regulating the epithelial-to-mesenchymal transition (EMT)

摘要

Oxygenated Polycyclic aromatic hydrocarbons (Oxy-PAHs) are widely distributed in the atmosphere, water, soil and sediments. Oxy-PAHs have been proved more carcinogenic than their parent PAHs, while there still lack of studies about the toxicological mechanism of Oxy-PAHs in epigenetic regulation. Our study revealed that exposure to Oxy-PAHs induced the invasion and migration of lung epithelial cells by the activation of epithelial-to-mesenchymal transition (EMT), including the up-regulation of Vimentin and alpha-smooth muscle actin (alpha-SMA) and the down-regulation of E-cadherin (E-cad). The reactive oxygen species (ROS) promoted histone acetylation mediated-Snail regulating the expression of E-cad after Oxy-PAHs treatment. Meanwhile, DNA methylation was also involved in epigenetic regulation of EMT. These results demonstrated a potential mechanism about Oxy-PAHs facilitate lung carcinogenesis by epigenetic regulation and suggested new ways for the treatment, improvement, and prevention of lung cancer caused by Oxy-PAHs environmental exposure. (C) 2019 Elsevier Ltd. All rights reserved.