Downregulation of miR-3127-5p promotes epithelial-mesenchymal transition via FZD4 regulation of Wnt/β-catenin signaling in non-small-cell lung cancer

Abstract

MiR-3127-5p has been implicated as a tumor-suppressive microRNA (miRNA) in non-small-cell lung cancer (NSCLC) and its expression was associated with tumor recurrence and poor prognosis. The aim of this study was to determine whether miR-3127-5p regulates epithelial-mesenchymal transition (EMT) in NSCLC, and to investigate the underlying mechanisms. Using qRT-PCR, we examined the expression levels of miR-3127-5p in a cohort of primary NSCLC specimens with and without distant metastasis. We further performed a series of in vitro and in vivo experiments to investigate the effects and underlying mechanism of miR-3127-5p on EMT, cell migration, invasion, and adhesion in NSCLC. We found that metastatic NSCLC tissues showed markedly downregulated miR-3127-5p expression. Transforming growth factor-β1 (TGF-β1) treatment induced EMT in A549 and H1299 cells, and downregulation of miR-3127-5p could result in the similar effect. Mechanically, we demonstrated that frizzled-4 (FZD4) is a target gene and miR-3127-5p exerts its effects by regulating the Wnt/β-catenin signaling. In addition, the expression levels of FZD4 and miR-3127-5p were also negatively associated in both clinical and xenografted tumors. Overall, these findings suggest that downregulation of miR-3127-5p promotes EMT through activating the Wnt/FZD4/β-catenin signaling pathway and may represent a therapeutic target for NSCLC metastasis.