组蛋白甲基化在皮肤癌中的作用：组蛋白甲基化修饰酶作为皮肤癌治疗的新靶点类。
Role of histone methylation in skin cancers: Histone methylation-modifying enzymes as a new class of targets for skin cancer treatment.
发表日期：2023 Feb 23
作者：
Natasha Christabella Sutopo, Ji Hye Kim, Jae Youl Cho
来源：
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
摘要：
组蛋白甲基化是最显著的表观遗传修饰之一，在基因转录中发挥着至关重要的作用，异常的组蛋白甲基化水平会导致肿瘤发生。组蛋白甲基化是可逆的酶依赖性反应，其中涉及到组蛋白甲基转移酶和去甲基酶。本文综述了这些组蛋白甲基化修饰酶在皮肤癌中的生物学和临床相关性。特别是详细讨论了组蛋白赖氨酸甲基转移酶、组蛋白精氨酸甲基转移酶、赖氨酸特异性去甲基化酶和JmjC去甲基化酶在皮肤癌中的作用。此外，我们总结了针对调节组蛋白甲基化修饰酶的多种表观遗传学抑制剂在基底细胞癌（BCC）、鳞状细胞癌（SCC）和黑色素瘤等皮肤癌中的疗效。最后，我们提出组蛋白甲基化修饰酶是治疗皮肤癌的下一代药物新靶点，并进一步提出了开发针对特定组蛋白甲基转移酶/去甲基酶的表观遗传学药物（epidrugs）的理由。版权所有©2023 Elsevier B.V.发表。
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 enzyme-dependent 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, lysine-specific 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.Copyright © 2023. Published by Elsevier B.V.