Rs2853677 modulates Snail1 binding to the TERT enhancer and affects lung adenocarcinoma susceptibility
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Xiaoting Li1,3,*, Xing Xu1,*, Jiali Fang1,*, Lin Wang1,*, Yanchao Mu1, Peng Zhang4, Zhi Yao1,2, Zhenyi Ma1, Zhe Liu1
1Department of Immunology, Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, China
2Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, Tianjin Medical University, Tianjin, China
3Department of Forensic Medicine, Tianjin Medical University, Tianjin, China
4Department of Clinical Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
*These authors contributed equally to this work
Zhe Liu, email: [email protected]
Peng Zhang, email: [email protected]
Keywords: rs2853677, Snail1, TERT, enhancer
Received: December 15, 2015 Accepted: April 28, 2016 Published: May 13, 2016
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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