miR-200b upregulation promotes migration of BEAS-2B cells following long-term exposure to cigarette smoke by targeting ETS1

Abstract

Cigarette smoking is the leading cause of all histo- logical types of lung cancer, and the role that microRNAs (miRNAs) serve in its pathogenesis is being increasingly recog- nized. The aim of the present study was to investigate the role of miR-200b on migration in cigarette smoke-induced malignant transformed cells. In the present study, miR-200b expression was found to be increased in cigarette smoke (CS)-exposed BEAS-2B cells, lung cancer cell lines and tumor tissue samples. Using wound healing and Transwell migration assays, the migratory ability was shown to be increased in miR-200b-overexpressing cells, whereas miR-200b knockdown resulted in reduced migration. Additionally, the expression of E-Cadherin was downregulated, whereas that of N-Cadherin was upregulated in miR-200b mimic-transfected cells, suggesting an increase in epithelial-mesenchymal transi- tion. Downstream, using four target gene prediction tools, six target genes of miR-200b were predicted, amongst which, ETS proto-oncogene 1 transcription factor (ETS1) was shown to be significantly associated with tumor invasion depth and negatively associated with miR-200b expression. The inter- action between miR-200b and ETS1 was confirmed using a dual-luciferase reporter assay. Using rescue experiments, the increased migratory ability of the miR-200b-overexpressing cells was reversed by ETS1 overexpression. In summary, this study showed that miR-200b overexpression serves a carci- nogenic role and promotes the migration of BEAS-2B cells following long-term exposure to CS by targeting ETS1.