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.