DNA羟甲基化在恶性黑素瘤的进展

DNA hydroxymethylation in malignant melanoma

DNA羟甲基化指在TET蛋白酶家族催化下,将5甲基胞嘧啶氧化成5羟甲基胞嘧啶的过程,是DNA主动去甲基化的关键中间步骤,主要通过动态调节DNA甲基化水平,影响基因表达.DNA羟甲基化过程可被TET蛋白、三羧酸循环相关酶、维生素C、微小RNA等多种因素调控.研究发现,和血液系统恶性肿瘤及多种实体肿瘤类似,恶性黑素瘤中同样存在5羟甲基胞嘧啶含量降低,DNA羟甲基化调控因素异常等现象,提示DNA羟甲基化可能与恶性黑素瘤的发生发展及预后等相关.

DNA hydroxymethylation refers to a chemical modification process in which 5-methylcytosine （5mC） is converted to 5-hydroxymethylcytosine （5hmC） by the ten-eleven translocation （TET） protein family.This conversion is an important intermediate step in active DNA demethylation,which can influence gene expressions by dynamically regulating DNA methylation levels.DNA hydroxymethylation can be modulated by TET proteins,the Krebs cycle-related enzymes,vitamin C,miRNAs,etc.Like patients with hematological malignancies or other solid cancers,those with cutaneous malignant melanoma have been reported to have decreased 5-hydroxymethylcytosine levels and abnormal DNA hydroxymethylation,hinting that DNA hydroxymethylation is related to the occurrence,development and prognosis of cutaneous malignant melanoma.