miRNA-193a Functions as a Tumor Suppressor Gene in Human Head and Neck Cancer; Development of a Novel Therapeutic Strategy

Head and neck squamous cell carcinoma (HNSCC) constitute a major public health burden with an annual incidence of almost 600,000 patients worldwide and a mean 5-year survival rate of less than 50%. The expression pattern of miRNA-193a in several cancers including leukemia, hepatocarcinoma, lung epithelial carcinoma and cervical adenocarcinoma cell lines showed down-regulation resulting from epigenetic silencing. The anti-oncogenic activity of miRNA-193a in Head and Neck cancer is not known. In our study, we found extremely high level of methylation rate on the promoter region in the pharynx originated cell lines (Fadu) compared to the tongue originated cells (SCC-9 and SCC-25) and to normal fibroblast resulted in significant decreases in the expression levels of miRNA-193a. Furthermore, we found that overexpression of miR-193a using gene therapy concept with Adenovirus inhibited the proliferation of Head and Neck cancer cells in vitro and in vivo. Our results indicated that transduction of Fadu cells with AD-miR-193a is significantly reduced cell viability in a dose and time dependent manner and induced apoptosis via activation of caspases. Moreover, in vivo studies using xenografts nude mice model revealed that treatment with Adeno-miR-193a inhibited tumour growth, thus tumor weight and volume were significantly reduced when compared to untreated-control group.

Our results reveal that miR-193a regulation plays an important role in Head and Neck cancer and suggest that sustained pre-miR-193a expression using Adenovirus could provide a promising strategy for the treatment of head and neck cancer.