Rs2853677 modulates Snail1 binding to the TERT enhancer and affects lung adenocarcinoma susceptibility.
Rs2853677 modulates Snail1 binding to the TERT enhancer and affects lung adenocarcinoma susceptibility.
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Rs2853677 调节 Snail1 与 TERT 增强子的结合并影响肺腺癌的易感性
DOI：
10.18632/oncotarget.9339
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发表时间：
2016-06-21
期刊：
影响因子：
--
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Li X;Xu X;Fang J;Wang L;Mu Y;Zhang P;Yao Z;Ma Z;Liu Z
全基因组关联研究（GWAS）表明，非编码区的SNP与遗传性癌症易感性相关。然而，一个单一SNP的效果是弱的。为了确定SNPs的潜在辅助因子，我们研究了SNPs影响肺癌易感性的潜在机制。我们发现rs 2853677位于一个TERT增强子的Snail 1结合位点内。当与TERT启动子并置时，该增强子增加TERT转录。Snail 1与增强子的结合破坏了增强子-启动子共定位并沉默了TERT转录。rs 2853677的高风险变体破坏Snail 1结合位点并响应于Snail 1上调而去抑制TERT表达，从而增加肺腺癌的易感性。我们的数据表明Snail 1可能是rs 2853677的辅助因子，用于预测肺腺癌的易感性和预后。
Genome wide association studies (GWAS) have shown that SNPs in non-coding regions are associated with inherited susceptibility to cancer. The effect of one single SNP, however, is weak. To identify potential co-factors of SNPs, we investigated the underlying mechanism by which SNPs affect lung cancer susceptibility. We found that rs2853677 is located within the Snail1 binding site in a TERT enhancer. This enhancer increases TERT transcription when juxtaposed to the TERT promoter. The binding of Snail1 to the enhancer disrupts enhancer-promoter colocalization and silences TERT transcription. The high risk variant of rs2853677 disrupts the Snail1 binding site and derepresses TERT expression in response to Snail1 upregulation, thus increasing lung adenocarcinoma susceptibility. Our data suggest that Snail1 may be a co-factor of rs2853677 for predicting lung adenocarcinoma susceptibility and prognosis.
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影响因子：
11.2
作者：
Ryan BM;Robles AI;McClary AC;Haznadar M;Bowman ED;Pine SR;Brown D;Khan M;Shiraishi K;Kohno T;Okayama H;Modali R;Yokota J;Harris CC
通讯作者：
Harris CC
影响因子：
5.8
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64.5
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3.1
作者：
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通讯作者：
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影响因子：
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作者：
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