MiR-451 inhibits cell growth and invasion by targeting MIF and is associated with survival in nasopharyngeal carcinoma

Abstract

BACKGROUND: MiRNAs play important roles in diverse biological processes including tumorigenesis. However, little is known about the function and mechanism of miR-451 in nasopharyngeal carcinoma (NPC). METHODS: Quantitative RT-PCR was used to quantify miR-451 expression in NPC cell lines and clinical tissues. Kaplan-Meier curves were used to estimate the association between miR-451 expression and survival. The MTT, colony formation, Transwell migration and invasion assays, and a xenograft model were performed. A miR-451 target was confirmed using luciferase reporter assays, quantitative RT-PCR, and Western blotting. RESULTS: MiR-451 was significantly downregulated in NPC cell lines and clinical tissues (P < 0.01). Patients with low expression of miR-451 had poorer overall survival (HR, 1.98; 95% CI, 1.16-3.34; P = 0.01) and disease-free survival (HR, 1.68; 95% CI, 1.07-2.62; P = 0.02) than patients with high expression. MiR-451 was an independent prognostic factor in NPC in multivariate Cox regression analysis. Ectopic expression of miR-451 suppressed cell viability, colony formation, and cell migration and invasion in vitro, and inhibited xenograft tumor growth in vivo. MIF was verified as a direct target of miR-451, and MIF regulated NPC cell growth and invasion. CONCLUSIONS: The newly identified miR-451/MIF pathway provides insight into NPC initiation and progression, and may represent a novel therapeutic target.