Role of histone methylation in skin cancers: Histone methylation-modifying enzymes as a new class of targets for skin cancer treatment

Histone methylation, one of the most prominent epigenetic modifications, plays a vital role in gene transcription, and aberrant histone methylation levels cause tumorigenesis. Histone methylation is a reversible enzymedependent reaction, and histone methyltransferases and demethylases are involved in this reaction. This review addresses the biological and clinical relevance of these histone methylation-modifying enzymes for skin cancer. In particular, the roles of histone lysine methyltransferases, histone arginine methyltransferase, lysinespecific demethylases, and JmjC demethylases in skin cancer are discussed in detail. In addition, we summarize the efficacy of several epigenetic inhibitors targeting histone methylation-modifying enzymes in cutaneous cancers, such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. In conclusion, we propose histone methylation-modifying enzymes as novel targets for next-generation pharmaceuticals in the treatment of skin cancers and further provide a rationale for the development of epigenetic drugs (epidrugs) that target specific histone methylases/demethylases in cutaneous tumors.

Automated summary

This review discusses the biological and clinical relevance of histone methylation-modifying enzymes in skin cancer, specifically examining the roles of histone lysine methyltransferases, histone arginine methyltransferase, lysine-specific demethylases, and JmjC demethylases. Additionally, the efficacy of epigenetic inhibitors targeting histone methylation-modifying enzymes in cutaneous cancers such as basal cell carcinoma, squamous cell carcinoma, and melanoma is summarized. The authors propose these enzymes as novel targets for next-generation pharmaceuticals in the treatment of skin cancers and provide a rationale for developing epigenetic drugs specifically targeting histone methylases/demethylases in cutaneous tumors.