机构：[1]National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi 710119, China[2]Department of Respiratory and Critical Care Medicine, Nanfang Hospital/The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China[3]Department of Respiratory Critical Care Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China内科科室呼吸内科昆明医科大学附属第一医院[4]Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China外科科室胸外科昆明医科大学附属第一医院[5]Provincial Demonstration Center for Experimental Biology Education, Shaanxi Normal University, Xi’an, Shaanxi 710119, China
Lung cancer is a common cancer in human and has presented significant genetic predisposition. Previous genome-wide association study observed that rs401681 within CLPTMIL (CLPTM1 like) was significantly associated with lung cancer. By analyzing 1000 genomes data for East Asian, we identified only one SNP in nearby region, rs402710, in high linkage disequilibrium with rs401681, which was also associated with lung cancer. However, the real causal SNP and mechanism for the association were still not clear. The following plasmid construction, mutagenesis, transient transfection and luciferase reading indicated that both SNPs could regulate gene expression in lung/bronchial epithelium Beas-2B cell line. By chromosome conformation capture, it was identified that the segment containing these two SNPs could interact with TERT (telomerase reverse transcriptase) promoter, thus indicating that these SNPs confer lung cancer risk by regulating TERT expression instead of CLPTM1L. Through chromatin immunoprecipitation, the transcript factors HNF4A (hepatocyte nuclear factor 4 alpha) and MAF1 (MAF1 homolog, negative regulator of RNA polymerase III) were recognized for the regions spanning rs401681 and rs402710, respectively. Our results uncovered a complete link between these two SNPs and lung cancer.
基金：
Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [GK201703031, GK201701005]; Yunnan Provincial Science and Technology Department [2017FE467-030]; High level talent training program in Yunnan [D-201662]; Kunming Medical University [2017FE467-030]
第一作者机构：[1]National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi 710119, China
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推荐引用方式(GB/T 7714)：
Yang Yu-Chen,Fu Wei-Ping,Zhang Jing,et al.rs401681 and rs402710 confer lung cancer susceptibility by regulating TERT expression instead of CLPTM1L in East Asian populations[J].CARCINOGENESIS.2018,39(10):1216-1221.doi:10.1093/carcin/bgy084.
APA：
Yang, Yu-Chen,Fu, Wei-Ping,Zhang, Jing,Zhong, Li,Cai, Shao-Xi&Sun, Chang.(2018).rs401681 and rs402710 confer lung cancer susceptibility by regulating TERT expression instead of CLPTM1L in East Asian populations.CARCINOGENESIS,39,(10)
MLA：
Yang, Yu-Chen,et al."rs401681 and rs402710 confer lung cancer susceptibility by regulating TERT expression instead of CLPTM1L in East Asian populations".CARCINOGENESIS 39..10(2018):1216-1221
