Repression of Smad4 by miR-205 moderates TGF-β-induced epithelial-mesenchymal transition in A549 cell lines

The TGF-beta Smad signaling pathway plays important roles in cancer cell proliferation, apoptosis, differentiation, angiogenesis and epithelial-mesenchymal transition (EMT), which is the key event in the early stages of cancer metastasis and enhances the capability of cell migration and invasion. Smad4 acts as the only Co-Smad of TGF/Smad signaling pathway and plays the key role in TGF-beta-mediated EMT. Nevertheless, the mRNA regulation mechanisms of Smad4 in human non-small cell lung cancer (NSCLC) remains largely unclear. Computational algorithms predicted that the 3'-UTR of Smad4 is a target of miR-205. Here, we validated that miR-205 could directly bind to 3'-UTR of Smad4 by luciferase assays. Moreover, we investigated the functional roles of miR-205 and its molecular link to Smad4 in lung cancer cells. In this study, we confirmed that overexpression of miR-205 suppressed the expression of Smad4, in turn, weakened the TGF-beta/Smad signaling pathway and inhibited TGF-beta/Smad4-induced EMT, invasion and migration ultimately. Furthermore, this study shows that miR-205 can serve as a promising therapeutic target of highly aggressive NSCLC.