期刊
ONCOTARGET
卷 7, 期 25, 页码 37825-37838出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.9339
关键词
rs2853677; Snail1; TERT; enhancer
资金
- National Natural Science Foundation of China [91519331, 31371295, 81572271, 81372307, 81572882]
- Ministry of Science and Technology of China [2014CB910104]
- Tianjin Municipal Science and Technology Commission [15JCZDJC34800]
- specialized Fund for the Doctoral Program of Higher Education [20121202110001]
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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