miR-181b-5p mediates TGF-β1-induced epithelial-to-mesenchymal transition in non-small cell lung cancer stem-like cells derived from lung adenocarcinoma A549 cells

The ability of non-small cell lung cancer (NSCLC) cells to invade and metastasize is associated with epithelialto-mesenchymal transition (EMT). The process of EMT is, at least in part, regulated by microRNAs. However, it is unknown whether microRNAs regulate EMT in cancer stem-like cells (CSLCs), or which microRNAs are involved. In the present study, we compared microRNA expression in A549 cells, TGF-beta 1-treated A549 cells, CSLCs characterized by the CD133(+)/CD326(+) phenotype, and TGF-beta 1-treated CSLCs. We found that miR-181b-5p expression was upregulated by TGF-beta 1. Moreover, the overexpression of the miR-181b-5p in A549 cells and CD133(+)/CD326(+) cells resulted in the down regulation of the E-cadherin and increased invasion and metastasis in vitro and in vivo. Accordingly, the knockdown of miR-181b-5p partially restored E-cadherin expression. These results suggest that miR-181b-5p regulates TGF-beta 1-induced EMT by targeting E-cadherin not only in normal A549 cells but also in CD133(+)/CD326(+) cells which have characteristics of CSLCs. Thus, miR-181b-5p represents a new therapeutic target in NSCLC.