A Genetic Polymorphism at miR-526b Binding- Site in the lincRNA- NR_ 024015 Exon Confers Risk of Esophageal Squamous Cell Carcinoma in a Population of North China
A Genetic Polymorphism at miR-526b Binding- Site in the lincRNA- NR_ 024015 Exon Confers Risk of Esophageal Squamous Cell Carcinoma in a Population of North China
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DOI：
10.1002/mc.22549
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发表时间：
2017-03-01
影响因子：
4.6
通讯作者：
Guo, Wei
中科院分区：
文献类型：
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作者：
Han, Lijie;Liu, Shengnan;Guo, Wei
食管鳞状细胞癌（ESCC）可能是由环境因素和遗传变异的组合引起的。本研究旨在评估lincRNA-NR_024015单倍型标签SNP（htSNPs）与ESCC风险之间的关联。我们在整个1469 bp的lincRNA-NR_024015基因座和该基因的2kb上游以及2kb下游区域选择htSNPs，并在581例ESCC病例和677名健康对照中进行病例对照研究，以测试功能性lincRNA-NR_024015 htSNPs对ESCC易感性的影响。在7个潜在的功能性htSNPs中，发现rs 8506 AA基因型与ESCC风险增加相关。进一步分层分析显示，男性患者和TNM III期和IV期患者的风险效应更明显。LincRNA-NR_024015主要表达于食管癌细胞的胞浆中。lincRNA-NR_024015在食管鳞癌组织中的表达水平显著高于相应正常组织，rs 8506基因型对lincRNA-NR_024015的表达具有基因型特异性影响。此外，rs 8506 G至A变体可能通过破坏hsa-miR-526 b与该位点的结合来影响lincRNA-NR_024015表达和功能。lincRNA-NR_024015和rs 8506 A等位基因的高表达水平与ESCC患者的生存率相关。提示lincRNA-NR_024015外显子rs 8506 G>A多态性可能是食管癌发生的遗传修饰因子，lincRNA-NR_024015可能是预测食管癌生物学行为的有用标记。(C)2016 Wiley Periodicals，Inc.
Esophageal squamous cell carcinoma (ESCC) may be caused by a combination of environmental factors and genetic variants. The present study was to evaluate the association between haplotype-tagging SNPs (htSNPs) of lincRNA-NR_024015 and the risk of ESCC. We selected htSNPs across the whole 1469bp lincRNA-NR_024015 locus and 2kb upstream as well as 2kb downstream regions of the gene and conducted a case-control study in 581 ESCC cases and 677 healthy controls to test the effects of functional lincRNA-NR_024015 htSNPs on ESCC susceptibility. Of the seven potential functional htSNPs, rs8506 AA genotype was found to be associated with increased risk of ESCC. Further stratification analysis showed that the risk effect was more pronounced in male patients and patients with TNM stage III and IV. LincRNA-NR_024015 was predominantly expressed in cytoplasm of esophageal cancer cells. The expression level of lincRNA-NR_024015 in ESCC tumor tissues was significantly higher than that in corresponding normal tissues and rs8506 genotype has a genotype-specific effect on lincRNA-NR_024015 expression. Furthermore, rs8506 G to A variant might influence lincRNA-NR_024015 expression and function by disrupting the binding of hsa-miR-526b to the site. High expression level of lincRNA-NR_024015 and rs8506 A allele were associated with poor ESCC patients' survival. These findings indicate that functional polymorphism rs8506 G>A in lincRNA-NR_024015 exon may be a genetic modifier for the development of ESCC and lincRNA-NR_024015 may be a useful marker for the prediction of the biological behavior of ESCC. (C) 2016 Wiley Periodicals, Inc.