TET家族DNA羟化酶与5-hmC在肿瘤中的作用机制的研究进展

DNA甲基化失调引起基因表达异常是表观遗传学的一个显著特点。目前已知，由DNA甲基转移酶（DNA methyltransferases，DMNTs）催化DNA甲基化，其酶基因突变或表达异常引起DNA甲基化水平的改变。近期研究发现了一种DNA去甲基化酶--TET（Ten-Eleventranslocation）家族DNA羟化酶，能通过多种途径催化5-甲基胞嘧啶（5．methylcytosine，5-mC）去甲基化，从而调控DNA基化的平衡。5-羟甲基胞嘧啶（5-hydroxymethylcytosine，5-hmC）作为DNA去甲基化多重步骤中重要的中间产物，其水平在肿瘤的发生和发展时期发生显著变化。该文从TET家族蛋白展开，介绍TET蛋白的结构、功能及作用机制以及多种人类肿瘤中丁E丁家族基因与5-hmC水平的相关性及其对肿瘤发生发展、诊断预后等临床意义的研究进展。

Research Advance of TET Family DNA Hydroxylase and 5-hmC in Neoplasm

Dysregulated DNA methylation followed by abnormal gene expression is an epigenetic feature in neoplasm. It is well known that DNA methylation is catalyzed by DNA methyltransferases, and the mutation of DNA methyltransferase gene and the aberrant expression influence the balance of DNA methylation. Recently, the enzyme for demethylating 5-methylcytosine were identified. TET （Ten-Eleven translocation） protein regulates the DNA demethylation pathway via various mechanisms. As a important intermediate product of DNA demethylation, the level of 5-hydroxymethylcytosine floats significantly in the period of tumor development. This review will de- tail the TET proteins from their structure, function, mechanism and introduce recent advances in researches on the relation between the biology significance of TET protein and 5-hmC regulation in various cancers. We also summarize the clinical significance of TET gene and 5-hmC in tumorigenesis and development.