MiR-646 suppresses proliferation and metastasis of non-small cell lung cancer by repressing FGF2 and CCND2.

ABSTRACT

MicroRNA-646 (miR-646) has been implicated in several other cancers; however, its functional mechanism in non-small cell lung cancer (NSCLC) remains unclear. In this study, we observed the downregulation of miR-646 expression in NSCLC tissues and cell lines. Low-level expression of miR-646 was associated with metastasis and stage of NSCLCs. Functional assays showed that overexpression of miR-646 could suppress NSCLC cell proliferation, clonogenicity, invasion, and inhibit epithelial-mesenchymal transition (EMT), whereas decreased miR-646 expression showed the opposite effects. Importantly, miR-646 overexpression attenuated in vivo tumor growth and metastasis in nude mice models. Mechanically, miR-646 directly targeted and suppressed fibroblast growth factor 2 (FGF2) and cyclin D2 (CCND2) expression. Reintroduction of FGF2 and CCND2 attenuated miR-646-mediated suppression of proliferation and invasion in NSCLC. Collectively, these results demonstrate that miR-646 acts as a tumor suppressor in NSCLC by targeting FGF2 and CCND2, and may serve as a therapeutic target for patients with NSCLC.