MiR-32 Functions as a Tumor Suppressor and Directly Targets EZH2 in Human Oral Squamous Cell Carcinoma

BACKGROUND: MicroRNA-32 (miR-32) is dysregulated in certain human malignancies and correlates with tumor progression. However, its expression and function in oral squamous cell carcinoma (OSCC) remain unclear. Thus, the aim of this study was to explore the effects of miR-32 expression on OSCC tumorigenesis and development. MATERIAL/METHODS: Real-time quantitative PCR was applied to evaluate the expression level of miR-32 in OSCC cell lines and primary tumor tissues. The association of miR-32 expression with clinicopathological factors and prognosis was also analyzed. In vitro cell proliferation, apoptosis, invasion, and migration assays were executed to elucidate biological effects of miR-32. Western blotting and luciferase assays were performed to confirm the regulation of EZH2 by miR-32. RESULTS: Down-regulation of miR-32 was found in OSCC tissues compared with corresponding noncancerous tissues (P<0.001). Decreased miR-32 expression was significantly associated with advanced T classifications, positive N classification, advanced TNM stage, and shorter overall survival (all P<0.05). Multivariate regression analysis corroborated that low-level expression of miR-32 was an independent unfavorable prognostic factor for OSCC patients. In vitro functional assays showed that overexpression of miR-32 reduced OSCC cell proliferation, migration, and invasion, and promoted cell apoptosis. In contrast, miR-32 knock-down resulted in an increase in cell growth and invasiveness. Finally, we identified EZH2 as the functional downstream target of miR-32 by directly targeting the 3′-UTR of EZH2. CONCLUSIONS: These findings indicate that miR-32 may act as a tumor suppressor in OSCC and could serve as a novel therapeutic agent for miR-based therapy.