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 1α (HIF-1α).
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-1α 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® insert system.
Results: miRNA-18a expression was significantly lower in OSCC tissue than in the adjacent normal tissue. In OSCC cell lines, HIF-1α 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-1α under hypoxic conditions relative to those abilities in cells treated only with miRNA-18a mimics.
Conclusions: miRNA-18a negatively affects HIF-1α expression and inhibits the metastasis of OSCC, thereby suggesting its potential as a therapeutic target for antimetastatic strategies in OSCC.
Keywords: HIF-1α; Hypoxia; Invasion; MicroRNA; Migration; Oral squamous cell carcinoma.
© 2022. The Author(s).