LAUSR

Arsenite is a well-documented human lung carcinogen but the detailed mechanisms of carcinogenesis remain unclear. In this study, human bronchial epithelial (16-HBE) cells were continuously exposed to 2.5μM arsenite for about 13 weeks to induce the phenotypes of malignant transformation. Our results showed that Nrf2 expression was gradually decreased whereas no significant change was observed on NF-κB activation with increased time of arsenite exposure. To test the roles of Nrf2-meidtaed oxidative damage in the arsenite-induced malignant transformation, we compared the levels of cGMP, PKG and oxidative damage-related indicators between arsenic-transformed cells and control cells. Our data demonstrated there were no significantly differences on the contents of cGMP, PKG, MDA and the production of ROS, but the levels of GSH and NO, the activities of SOD, tNOS and iNOS were significantly enhanced in the arsenic-transformed cells. Importantly, Nrf2 inactivation could be modulated by miR-155, and inhibition of miR-155 remarkably attenuated the malignant phenotypes and promoted apoptotic cell death in the arsenic-transformed cells. Together, our findings provide the novel mechanism that miR-155 may regulate arsenite-induced cell malignant transformation by targeting Nrf2-mediated oxidative damage, indicating that inhibition of miR-155 may be a potential strategy against lung carcinogenesis of arsenite.