Moreover, an increase of de novo DNA methylation activity of DNMT3B following its interaction with NEDDylated CUL4A (CUL4A-NEDD8) could be involved in local DNA hypermethylation and was reported in tissues (e.g., breast cancer (BC) and hepatoma) overexpressing CUL4A [80]. Here, CUL4A is linked to hepatocellular carcinoma.