Tumor development is associated with decrease of TET gene expression and 5-methylcytosine hydroxylation.
Tumor development is associated with decrease of TET gene expression and 5-methylcytosine hydroxylation.
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DOI：
10.1038/onc.2012.67
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发表时间：
2013-01-31
期刊：
影响因子：
8
通讯作者：
Xiong, Y.
中科院分区：
文献类型：
--
作者：
Yang, H.;Liu, Y.;Bai, F.;Zhang, J-Y;Ma, S-H;Liu, J.;Xu, Z-D;Zhu, H-G;Ling, Z-Q;Ye, D.;Guan, K-L;Xiong, Y.
α-酮戊二酸（α-KG）依赖性双加氧酶的泰特（ten-eleven translocation）家族催化5-甲基胞嘧啶（5 mC）依次氧化为5-羟甲基胞嘧啶（5 hmC）、5-甲酰基胞嘧啶和5-羧基胞嘧啶，最终导致DNA去甲基化。TET 2基因是一种真正的肿瘤抑制基因，在白血病中经常发生突变，在IDH 1/2突变的肿瘤中，泰特酶活性受到α-KG拮抗剂2-羟基戊二酸的抑制，将5 mC氧化与癌症发展联系起来。我们在这里报告说，5 hmC的水平显着降低，在人类乳腺癌，肝癌，肺癌，胰腺癌和前列腺癌相比，匹配的周围正常组织。与5 hmC降低相关的是所有三种泰特基因表达的显著降低，揭示了癌细胞中5 hmC降低的可能机制。在不同的基因工程小鼠模型中，在肿瘤发展过程中也观察到5 hmC的降低。总之，我们的结果将5 hmC确定为生物标志物，其减少与肿瘤发展广泛而紧密相关。
The TET (ten–eleven translocation) family of α-ketoglutarate (α-KG)-dependent dioxygenases catalyzes the sequential oxidation of 5-methylcytosine (5mC) to 5-hydroxymethyl-cytosine (5hmC), 5-formylcytosine and 5-carboxylcytosine, leading to eventual DNA demethylation. The TET2 gene is a bona fide tumor suppressor frequently mutated in leukemia, and TET enzyme activity is inhibited in IDH1/2-mutated tumors by the oncometabolite 2-hydroxyglutarate, an antagonist of α-KG, linking 5mC oxidation to cancer development. We report here that the levels of 5hmC are dramatically reduced in human breast, liver, lung, pancreatic and prostate cancers when compared with the matched surrounding normal tissues. Associated with the 5hmC decrease is the substantial reduction of the expression of all three TET genes, revealing a possible mechanism for the reduced 5hmC in cancer cells. The decrease of 5hmC was also observed during tumor development in different genetically engineered mouse models. Together, our results identify 5hmC as a biomarker whose decrease is broadly and tightly associated with tumor development.
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DOI：
10.1126/science.1170944
发表时间：
2009-04-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Zhao S;Lin Y;Xu W;Jiang W;Zha Z;Wang P;Yu W;Li Z;Gong L;Peng Y;Ding J;Lei Q;Guan KL;Xiong Y
通讯作者：
Xiong Y
影响因子：
64.8
作者：
通讯作者：
--
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：
30.8
作者：
Langemeijer, Saskia M. C.;Kuiper, Roland P.;Jansen, Joop H.
通讯作者：
Jansen, Joop H.