Li Feng-Juan, Li Li-Ming, Zhang Rui-Hua, Xu Cui, Zhou Pan, Long Jia, Hu Gang, Jiang Ming-Jun
aJiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College bLaboratory Centre of Life Science, College of Life Science, Nanjing Agricultural University, Nanjing cDepartment of Dermatology, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China.
Melanoma Res. 2017 Jun;27(3):175-179. doi: 10.1097/CMR.0000000000000349.
Malignant melanoma is a highly aggressive neoplasia of melanocytic origin. In part because of the lack of effective treatment methods, the incidence and mortality rates of this disease continue to increase. Rapidly accumulating evidence suggests that dysregulation of epigenetic mechanisms, including DNA methylation/demethylation, chromatin modification, and remodeling, and diverse activities of noncoding RNAs, play a central role in the pathogenesis of melanoma. The epigenetic mark 5-hydroxymethylcytosine (5-hmC) has attracted interest since 2009, when it was shown that ten-eleven translocation proteins can enzymatically convert 5-methylcytosine into 5-hmC, a key intermediate of DNA demethylation. Factors that regulate DNA hydroxymethylation are frequently altered in cancer, leading to deregulation of 5-hmC levels. In this review, we will discuss the relationship between melanoma and DNA hydroxymethylation, the regulation of DNA hydroxymethylation, and defects in this pathway in melanoma.
恶性黑色素瘤是一种起源于黑素细胞的高度侵袭性肿瘤。部分由于缺乏有效的治疗方法，这种疾病的发病率和死亡率持续上升。迅速积累的证据表明，表观遗传机制的失调，包括DNA甲基化/去甲基化、染色质修饰和重塑，以及非编码RNA的多种活动，在黑色素瘤的发病机制中起核心作用。自2009年以来，表观遗传标记5-羟甲基胞嘧啶（5-hmC）引起了人们的关注，当时研究表明，10-11易位蛋白可以将5-甲基胞嘧啶酶促转化为5-hmC，这是DNA去甲基化的关键中间体。调节DNA羟甲基化的因素在癌症中经常发生改变，导致5-hmC水平失调。在这篇综述中，我们将讨论黑色素瘤与DNA羟甲基化之间的关系、DNA羟甲基化的调节以及黑色素瘤中该途径的缺陷。
