Chronic arsenic treatment induces epithelial-mesenchymal transition (EMT) and promotes tumorigenicity, but the mechanism is unclear. MiR-100 has been shown to be involved in this biologic process. In this study, we hypothesize that inactivation of miR-100 combined with low concentration of arsenic exposure could promote the malignant transformation of human bronchial epithelial cells (BEAS-2B cell) by promoting EMT. To test this hypothesis, BEAS-2B cells were treated with low-dose of As2O3 chronically, and lentiviral vectors were used to mediate the inhibition of miR-100 expression. Flow cytometry, cloning formation, and transwell assays were used to examine cell cycle progression, cell proliferation, and cell migration, respectively. The mouse xenograft model was used to investigate the cell malignant growth in vivo, and western blot was used to detect EMT related marker expressions. Our results showed that, the inactivation of miR-100 combined with arsenic treatment significantly promoted the proliferation, viability, and migration of BEAS-2B cells in vitro, and tumorigenesis in vivo. Consistently, the EMT related marker expressions were also significantly increased in corresponding groups. Our data indicate that inactivation of miR-100 combined with chronic arsenic treatment promotes tumorigenicity of BEAS-2B cells via activation of EMT. This novel insight may help us to better understand the pathogenesis of arsenic carcinogenesis.
Keywords: Carcinogenesis; lung cancer; miR-100; micro RNA.