A. NUAK1 expression was examined by immunohistochemistry in 54 HNSCC cases. Representative pictures of NUAK1 positive or negative HNSCC case are shown. B. The graph shows the number of cases with or without NUAK1 expression in each grade of the YK classification (YK-2, -3, -4C, and -4D). C. Schematic model of the role of miR-203 in HNSCC. In HNSCC cells with epithelial phenotype, miR-203 suppresses the expression of NUAK1 and SNAI2. In HNSCC cells with EMT phenotype, miR-203 is downregulated by hypermethylation. Therefore, miR-203 cannot suppress the expression of NUAK1 and SNAI2. Elevated expression of NUAK1 may induce the invasion of HNSCC cells. In addition, the miR-200 family (miR-200a, -200b, -200c, and -141) is also downregulated and target genes including ZEB1, ZEB2, SNAI1, etc. are upregulated. Downregulation of miR-203 may be caused by downregulation of the miR-200 family and/or upregulation of SNAI1/SNAI2 and ZEB1/ZEB2. Elevated expression of NUAK1, ZEB1, ZEB2, SNAI1, and SNAI2 may induce EMT in HNSCC cells.