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Asbestos-Induced Lung Cancer-Associated SNP rs13383928 Regulates PTH2R Expression in Lung Tissue
Human Heredity ( IF 1.8 ) Pub Date : 2021-02-05 , DOI: 10.1159/000513291
Yuan-Qing Meng , Qiang Shi , Si-Jing Zhu , Guang-Huan He , Shi-Jiao Zhang , Chang Sun

Background: Lung cancer is one of the most common malignant tumors, and asbestos exposure was suggested to contribute to a proportion of lung cancer cases. Previous genome-wide gene-environment interaction analysis reported that rs13383928 was associated with asbestos-related lung cancer. However, the mechanism of this association was still unclear. Methods: In the present study, we retrieved the genotype data from the 1,000 Genomes Project on single-nucleotide polymorphisms (SNPs) surrounding rs13383928 and analyzed the linkage disequilibrium (LD) pattern of this region. Further functional genomics analyses were performed. Results: The result indicated that no other SNPs were in LD with rs13383928, suggesting that rs13383928 is the causal one. The following dual luciferase assay disclosed that the T allele of rs13383928 presented significantly higher enhancer activity than G in lung cells, thus verifying that this SNP was functional in the lung. Through chromosome conformation capture, the PTH2R (parathyroid hormone 2 receptor)promoter was identified to interact with the segment surrounding rs13383928. By chromatin immunoprecipitation, it was observed that the region spanning rs13383928 could bind transcription factor FOXJ2 (forkhead box J2). Conclusion: Our functional genomics evidence supports a link between rs13383928 and asbestos-related lung cancer through regulating PTH2R.
Hum Hered


中文翻译:

石棉诱导的肺癌相关SNP rs13383928调节肺组织中PTH2R的表达

背景:肺癌是最常见的恶性肿瘤之一,石棉接触被认为是导致肺癌病例的一部分。先前的全基因组全基因-环境相互作用分析报告说,rs13383928与石棉相关的肺癌有关。但是,这种关联的机制仍不清楚。方法:在本研究中,我们从1000个基因组计划的rs13383928周围的单核苷酸多态性(SNP)中检索了基因型数据,并分析了该区域的连锁不平衡(LD)模式。进行了进一步的功能基因组学分析。结果:结果表明,rs13383928在LD中没有其他SNP,这表明rs13383928是有原因的。以下双重荧光素酶测定法揭示了rs13383928的T等位基因在肺细胞中表现出比G高得多的增强子活性,从而证实了该SNP在肺中具有功能。通过染色体构象捕获,PTH2R(甲状旁腺激素2受体)启动子被鉴定为与rs13383928周围的节段相互作用。通过染色质免疫沉淀,观察到跨越rs13383928的区域可以结合转录因子FOXJ2(前额框J2)。结论:我们的功能基因组学证据通过调节PTH2R支持rs13383928与石棉相关的肺癌之间的联系。
嗡嗡声
更新日期:2021-02-05
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