The Jumonji domain-containing protein 3 (JMJD3), a histone H3K27 demethylase, which is highly expressed in aggressive hepatocellular carcinoma cells, interacts with Smad3 [78], and catalyzes the transition of H3K27me3 and H3K27me2 to H3K27me1 on the Snail2/Slug promoter, switching the chromatin from a repressive to an active conformation. This evidence concerns the gene SNAI2 and hepatocellular carcinoma.