Dysregulated miR-363 affects head and neck cancer invasion and metastasis by targeting podoplanin

Head and neck squamous cell carcinoma (HNSCC) is characterised by an elevated capacity for tumour invasion and lymph node metastasis and the cause remains to be determined. Recent studies suggest that microRNAs can regulate the evolution of malignant behaviours by regulating multiple target genes. In this study, we have first confirmed that miR-363 is down-regulated in HNSCC tissues with lymph node metastasis and cell lines with highly invasive capacity. We used bioinformatics, cellular and molecular methods to predict and prove that miR-363 directly targeted to podoplanin (PDPN) and caused up-regulation of PDPN in HNSCC. MSP assay showed that DNA promoter methylation was involved in silencing the miR-363 in HNSCC. Furthermore, we provided evidence to demonstrate that PDPN dysregulation caused by down-regulation of miR-363 contributes to HNSCC invasion and metastasis. These data reveal a key role of miR-363-PDPN in HNSCC metastasis and support biological and clinical links between miR-363-PDPN and HNSCC.