MicroRNA-16 Represses TGF-β1-induced Epithelial-to-Mesenchymal Transition in Human Lung Adenocarcinoma Cell Line.

Abstract

The transforming growth factor-beta1 (TGF-β1)-induced epithelial-tomesenchymal transition (EMT) has a crucial effect on the progression and metastasis of lung cancer cells. The purpose of this study was to investigate whether microRNA (miR)-16 can suppress TGF-β1-induced EMT and proliferation in human lung adenocarcinoma cell line (A549). Quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expression of miR-16. The hallmarks of EMT were assessed by RT-qPCR, Western blotting, and cell proliferation assay. A bioinformatics tool was used to identify the putative target of miR-16. The activation of TGF-β1/Smad3 signaling was analysed using Western blotting. Our results showed that miR-16 expression was significantly down-regulated by TGF-β1 in A549 cells. Moreover, agomir of miR-16 suppressed TGF-β1-induced EMT and cell proliferation. Computational algorithms predicted that the 3'-untranslated regions (3'-UTRs) of Smad3 are direct targets of miR-16. In addition, miR-16 mimic was found to inhibit the TGF-β1-induced activation of the TGF-β1/Smad3 pathway, suggesting that miR-16 may function partly through regulating Smad3. Our results demonstrated that overexpression of miR-16 suppressed the expression and activation of Smad3, and ultimately inhibited TGF-β1-induced EMT and proliferation in A549 cells. The present findings support further investigation of the anti-cancer effect of miR-16 in animal models of lung cancer to validate the therapeutic potential.