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.