MicroRNA-18a regulates the metastatic properties of oral squamous cell carcinoma cells via HIF-1alpha expression.

BACKGROUND: Rapid metastasis of oral squamous cell carcinoma (OSCC) is associated with a poor prognosis and a high mortality rate. However, the molecular mechanisms underlying OSCC metastasis have not been fully elucidated. Although deregulated expression of microRNA (miRNA) has a crucial role in malignant cancer progression, the biological function of miRNA in OSCC progression remains unclear. This study aimed to investigate the function of miRNA-18a in OSCC metastatic regulation via hypoxia-inducible factor 1alpha (HIF-1alpha). METHODS: miRNA-18a-5p (miRNA-18a) expressions in patients with OSCC (n = 39) and in OSCC cell lines (e.g., YD-10B and HSC-2 cells) were analyzed using quantitative real-time polymerase chain reaction. HIF-1alpha protein expressions in OSCC cells treated with miRNA-18a mimics or combined with cobalt chloride were analyzed using western blotting. The miRNA-18a expression-dependent proliferation and invasion abilities of OSCC cells were analyzed using MTT assay, EdU assay, and a Transwell(R) insert system. RESULTS: miRNA-18a expression was significantly lower in OSCC tissue than in the adjacent normal tissue. In OSCC cell lines, HIF-1alpha expression was significantly decreased by miRNA-18a mimic treatment. Furthermore, the migration and invasion abilities of OSCC cells were significantly decreased by miRNA-18a mimics and significantly increased by the overexpression of HIF-1alpha under hypoxic conditions relative to those abilities in cells treated only with miRNA-18a mimics. CONCLUSIONS: miRNA-18a negatively affects HIF-1alpha expression and inhibits the metastasis of OSCC, thereby suggesting its potential as a therapeutic target for antimetastatic strategies in OSCC.