SET and MYND domain containing protein 3 in cancer.

Lysine methylation plays a vital role in histone modification. Deregulations of lysine methyltransferases and demethylases have been frequently observed in human cancers. The SET and MYND domain containing protein 3 (SMYD3) is a novel histone lysine methyltransferase and it functions by regulating chromatin during the development of myocardial and skeletal muscle. It has been recently unveiled to play significant roles in human cancer genesis and progression via regulating various key cancer-associated genes and pathways and promoting cell proliferation and migration. Upregulation of SMYD3 expression is present in multiple cancer types, suggesting it as a potential prognostic marker. Herein the structure, substrates and targets of SMYD3, and its effects on initiation, invasion and metastasis of diverse tumors (e.g., esophageal squamous cell carcinoma, gastric cancer, hepatocellular carcinoma, cholangiocarcinoma, breast cancer, prostate cancer, and leukemia) are systematically reviewed, providing clues for the development of novel SMYD3-specific personalized anti-cancer therapy. SMYD3 inhibitors (e.g., BCI-121 and novobiocin) could hopefully fight against tumors with efficacy.