Dual-receptor (EGFR and C-Met) Inhibition by Tumor-Suppressive Mir-1 and Mir-206 in Head and Neck Squamous Cell Carcinoma

Our studies of microRNA (miRNA) expression signatures have shown that microRNA-1 ( miR-1 ) and microRNA-206 ( miR-206 ) were downregulated in head and neck squamous cell carcinoma (HNSCC) clinical specimens. The seed sequences of these miRNAs are identical, suggesting that the identification of the molecular targets regulated by miR-1 and miR-206 will provide new insights into novel mechanisms of HNSCC pathogenesis. Our present data showed that restoration of miR-1 and miR-206 significantly inhibited HNSCC cells’ aggressiveness. A combination of gene expression data and in silico analysis revealed that several pathways (‘pathway in cancer’, ‘focal adhesion pathway’, ‘MAPK signaling pathway’, ‘regulation of actin cytoskeleton pathway’ and ‘ECM–receptor interaction pathway’) were regulated by miR-1 and miR-206 . Among them, we found that two growth factor receptors, epidermal growth factor receptor ( EGFR ) and hepatocyte growth factor receptor (c- MET ), were directly regulated by both miR-1 and miR-206 in HNSCC cells. Also, downstream oncogenic signaling of these receptors was reduced by restoration of miR-1 or miR-206 expression. Moreover, overexpression of EGFR and c-MET was observed in HNSCC clinical specimens. The identification of targets modulated by tumor-suppressive miR-1 and miR-206 may lead to a better understanding of molecular pathogenesis of HNSCC.