A functional variant in TNXB promoter associates with the risk of esophageal squamous-cell carcinoma.,Molecular Carcinogenesis

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A functional variant in TNXB promoter associates with the risk of esophageal squamous-cell carcinoma.
Molecular Carcinogenesis ( IF 3.0 ) Pub Date : 2020-02-13 , DOI: 10.1002/mc.23166
Nan Yang ₁ , Jianbo Tian ₁ , Xiaoyang Wang ₁ , Shufang Mei ₁ , Danyi Zou ₁ , Xiating Peng ₁ , Ying Zhu ₁ , Yang Yang ₁ , Yajie Gong ₁ , Juntao Ke ₁ , Rong Zhong ₁ , Jiang Chang ₁ , Xiaoping Miao ₁

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Our previous study identified a tag single-nucleotide polymorphism (SNP) rs204900 in TNXB associated with risk of esophageal squamous-cell carcinoma (ESCC) in the Chinese population. However, the functional role of TNXB and causal variants had not been interrogated in that study. In the present study, we explored the effects of TNXB expression in the development of ESCC and searched for functional variants in this gene. We found TNXB was downregulated in ESCC tumors. Using small interfering RNAs and CRISPR-Cas9 methods, we identified that both knockdown and knockout of TNXB significantly promoted ESCC cell growth in vitro, suggesting a tumor suppressor role of this gene in ESCC. Through further fine-mapping analysis, we identified that a noncoding variant in the promoter of TNXB, rs411337, predisposed to ESCC risk (odds ratio = 1.36, 95% confidence interval: 1.22-1.51, P = 9.10 × 10-9 ). These findings revealed the functional mechanism of TNXB in the development of ESCC and may contribute to the prevention and treatment of this disease in the future.

更新日期：2020-03-30

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