Decrease of 5-hydroxymethylcytosine is associated with progression of hepatocellular carcinoma through downregulation of TET1.
Decrease of 5-hydroxymethylcytosine is associated with progression of hepatocellular carcinoma through downregulation of TET1.
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DOI：
10.1371/journal.pone.0062828
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Qian C
中科院分区：
文献类型：
--
作者：
Liu C;Liu L;Chen X;Shen J;Shan J;Xu Y;Yang Z;Wu L;Xia F;Bie P;Cui Y;Bian XW;Qian C
DNA甲基化是一种重要的表观遗传修饰，在癌症中经常发生改变。泰特家族酶将5-甲基胞嘧啶（5 mC）转化为5-羟甲基胞嘧啶（5 hmC）在胚胎干细胞的发育、衰老和疾病中发挥着重要的生物学功能。最近的报告显示，5 hmC的水平在各种类型的癌症中改变。然而，肝细胞癌（HCC）中5 hmC水平的变化及其与临床结局的关系尚不清楚。在这里，我们报道了5 hmC水平降低，在肝癌组织中，与非肿瘤组织相比。临床病理分析显示，HCC患者5 hmC水平降低与肿瘤大小、AFP水平及总生存率相关。我们还发现非肿瘤组织中5 hmC水平的降低与手术切除后第一年的肿瘤复发相关。在致癌物DEN诱导的HCC动物模型中，我们发现在诱导期间肝脏中的5 hmC水平逐渐降低。随着肿瘤的发展，肿瘤组织中的5 hmC进一步降低。相反，在HCC组织中5 mC水平升高，并且升高的5 mC水平与包膜侵犯、血管血栓形成、肿瘤复发和总生存率相关。此外，我们的数据显示TET 1的表达在HCC中下调，而TET 2和TET 3则没有。因此，5 hmC可作为HCC的预后指标，TET 1表达降低可能是HCC中5 hmC丢失的机制之一。
DNA methylation is an important epigenetic modification and is frequently altered in cancer. Convert of 5-methylcytosine (5 mC) to 5-hydroxymethylcytosine (5 hmC) by ten-eleven translocation (TET) family enzymes plays important biological functions in embryonic stem cells, development, aging and disease. Recent reports showed that level of 5 hmC was altered in various types of cancers. However, the change of 5 hmC level in hepatocellular carcinoma (HCC) and association with clinical outcome were not well defined. Here, we reported that level of 5 hmC was decreased in HCC tissues, as compared with non-tumor tissues. Clincopathological analysis showed the decreased level of 5 hmC in HCC was associated with tumor size, AFP level and poor overall survival. We also found that the decreased level of 5 hmC in non-tumor tissues was associated with tumor recurrence in the first year after surgical resection. In an animal model with carcinogen DEN-induced HCC, we found that the level of 5 hmC was gradually decreased in the livers during the period of induction. There was further reduction of 5 hmC in tumor tissues when tumors were developed. In contrast, level of 5 mC was increased in HCC tissues and the increased 5 mC level was associated with capsular invasion, vascular thrombosis, tumor recurrence and overall survival. Furthermore, our data showed that expression of TET1, but not TET2 and TET3, was downregulated in HCC. Taken together, our data indicated 5 hmC may be served as a prognostic marker for HCC and the decreased expression of TET1 is likely one of the mechanisms underlying 5 hmC loss in HCC.
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影响因子：
50.3
作者：
Xu W;Yang H;Liu Y;Yang Y;Wang P;Kim SH;Ito S;Yang C;Wang P;Xiao MT;Liu LX;Jiang WQ;Liu J;Zhang JY;Wang B;Frye S;Zhang Y;Xu YH;Lei QY;Guan KL;Zhao SM;Xiong Y
通讯作者：
Xiong Y
影响因子：
50.3
作者：
Figueroa ME;Abdel-Wahab O;Lu C;Ward PS;Patel J;Shih A;Li Y;Bhagwat N;Vasanthakumar A;Fernandez HF;Tallman MS;Sun Z;Wolniak K;Peeters JK;Liu W;Choe SE;Fantin VR;Paietta E;Löwenberg B;Licht JD;Godley LA;Delwel R;Valk PJ;Thompson CB;Levine RL;Melnick A
通讯作者：
Melnick A
影响因子：
3.7
作者：
Globisch D;Münzel M;Müller M;Michalakis S;Wagner M;Koch S;Brückl T;Biel M;Carell T
通讯作者：
Carell T
影响因子：
6
作者：
Lee, S;Lee, HJ;Kang, GH
通讯作者：
Kang, GH
影响因子：
16
作者：
Xu Y;Wu F;Tan L;Kong L;Xiong L;Deng J;Barbera AJ;Zheng L;Zhang H;Huang S;Min J;Nicholson T;Chen T;Xu G;Shi Y;Zhang K;Shi YG
通讯作者：
Shi YG