MicroRNA-198 suppresses tumour growth and metastasis in oral squamous cell carcinoma by targeting CDK4

MicroRNAs (miRNAs/miR) often contribute to the progression of oral squamous cell carcinoma (OSCC) via the regulation of mRNA. The present study aimed to investigate the role of miR-198 in OSCC pathogenesis and explore the underlying mechanism. Reverse transcription-quantitative (RT-q)PCR was performed to determine miR-198 expression in OSCC tissues and cell lines, and univariate and multivariate analyses were applied to evaluate the survival of patients with OSCC. The effects of miR-198 on OSCC cell lines were studied in vitro and in vivo. A set of epithelial-mesenchymal transition (EMT) markers were detected to determine whether miR-198 was involved in EMT. Lastly, using luciferase assays, a novel target of miR-198 was identified and the effect of the new target gene of miR-198 on cell proliferation and invasion was also studied. It was identified that miR-198 expression was decreased in OSCC tissues and cell lines, and low expression of miR-198 was associated with poor overall survival and disease-free survival. Overexpression of miR-198 appeared to significantly inhibit the proliferation, invasion and EMT of OSCC cells. Moreover, the luciferase assay results showed that miR-198 interacted with cyclin-dependent kinase 4 (CDK4) by directly targeting the miRNA-binding site in the CDK4 sequence, and RT-qPCR results showed that CDK4 expression was increased in OSCC tissues and cell lines. In addition, transfection of small interfering RNA against CDK4 in OSCC cells showed similar inhibitory effects on cell proliferation, invasion and EMT, whereas CDK4 overexpression in OSCC cells partially reversed the inhibitory effects of the miR-198 mimic. The present results indicated that miR-198 suppressed OSCC tumour growth and metastasis by directly targeting CDK4 expression. Thus, miR-198 may be a potential therapeutic target in the treatment of OSCC.

Automated summary

miR-198 downregulation in OSCC tissues and cell lines is associated with poor overall survival and disease-free survival. Overexpression of miR-198 significantly inhibits proliferation, invasion, and EMT of OSCC cells. Luciferase assay results demonstrate that miR-198 interacts with CDK4 by directly targeting its binding site in the CDK4 sequence.