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 histological types of lung cancer, and the role that microRNAs (miRNAs) serve in its pathogenesis is being increasingly recognized. 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 transition. 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 interaction 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 carcinogenic role and promotes the migration of BEAS-2B cells following long-term exposure to CS by targeting ETS1.