TET1 Depletion Induces Aberrant CpG Methylation in Colorectal Cancer Cells.
TET1 Depletion Induces Aberrant CpG Methylation in Colorectal Cancer Cells.
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DOI：
10.1371/journal.pone.0168281
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Suzuki H
中科院分区：
文献类型：
--
作者：
Kai M;Niinuma T;Kitajima H;Yamamoto E;Harada T;Aoki H;Maruyama R;Toyota M;Sasaki Y;Sugai T;Tokino T;Nakase H;Suzuki H
异常DNA甲基化在结直肠癌（CRC）中常见，但其潜在机制尚未完全了解。5-在CRC中，羟甲基胞嘧啶水平和TET 1表达均降低，而据报道TET 1的表观遗传沉默与CpG岛甲基化表型相关。在本研究中，我们的目的是澄清TET 1的损失和异常的DNA甲基化在结直肠癌之间的关系。使用表达高水平TET 1的Colo 320 DM细胞和以与正常结肠组织中相似的水平表达TET 1的HCT 116细胞建立稳定的TET 1敲低克隆。Infinium HumanMethylation 450 BeadChip检测显示TET 1缺失的Colo 320 DM细胞中超过10，000个CpG位点的5-甲基胞嘧啶水平升高。在基因组内的各个位置观察到DNA甲基化的变化，包括启动子、基因体和基因间区域，并且改变的甲基化影响基因子集的表达。相比之下，TET 1敲低并不显著影响HCT 116细胞中的DNA甲基化。然而，TET 1消耗与5-氮杂-2 '-脱氧胞苷对两种细胞系中基因表达谱的减弱作用有关。这些结果表明TET 1的缺失可能诱导异常的DNA甲基化，并可能减弱5-氮杂-2 '-脱氧胞苷在CRC细胞中的作用。
Aberrant DNA methylation is commonly observed in colorectal cancer (CRC), but the underlying mechanism is not fully understood. 5-hydroxymethylcytosine levels and TET1 expression are both reduced in CRC, while epigenetic silencing of TET1 is reportedly associated with the CpG island methylator phenotype. In the present study, we aimed to clarify the relationship between loss of TET1 and aberrant DNA methylation in CRC. Stable TET1 knockdown clones were established using Colo320DM cells, which express high levels of TET1, and HCT116 cells, which express TET1 at a level similar to that in normal colonic tissue. Infinium HumanMethylation450 BeadChip assays revealed increased levels of 5-methylcytosine at more than 10,000 CpG sites in TET1-depleted Colo320DM cells. Changes in DNA methylation were observed at various positions within the genome, including promoters, gene bodies and intergenic regions, and the altered methylation affected expression of a subset of genes. By contrast, TET1 knockdown did not significantly affect DNA methylation in HCT116 cells. However, TET1 depletion was associated with attenuated effects of 5-aza-2’-deoxycytidine on gene expression profiles in both cell lines. These results suggest that loss of TET1 may induce aberrant DNA methylation and may attenuate the effect of 5-aza-2’-deoxycytidine in CRC cells.
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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：
6
作者：
Bharadwaj, Alamelu G.;Kovar, Joy L.;Simpson, Melanie A.
通讯作者：
Simpson, Melanie A.
DOI：
10.1016/j.bbrc.2014.10.016
发表时间：
2014-10-31
影响因子：
3.1
作者：
Dong, Wenjie;Shen, Ruizhe;Cheng, Shidan
通讯作者：
Cheng, Shidan
影响因子：
2.7
作者：
Mirmohammadsadegh, A;Baer, A;Hengge, UR
通讯作者：
Hengge, UR
影响因子：
3.6
作者：
Dong, Xingyu;Deng, Qingshan;Xu, Ruxiang
通讯作者：
Xu, Ruxiang