Furthermore, MAPK signal aberrant activation by BRAFV600E has also been demonstrated to increase the level of H3K27me3 through increasing the expression of Ezh2 in thyroid cancer.15 Conversely, the decrease of H3K27me3 via reducing the expression of EZH2 by MAPKi was fulfilled in thyroid cancer, and the differentiation markers in melanoma and neuroblastoma could be increased by EZH2 knockdown.12, 15, 16 However, the differentiation efficacy of EZH2 inhibitor alone or combined with MAPKi in thyroid cancer remains unknown. This evidence concerns the gene EZH2 and melanoma.