Integrating apaQTL and eQTL analysis identifies a potential causal variant associated with lung adenocarcinoma risk in the Chinese population.

整合 apaQTL 和 eQTL 分析确定了中国人群中与肺腺癌风险相关的潜在因果变异。

• 影响指数: 6.548
• 发表时间: 2024 Jul 13
• 来源期刊: Commun Biol
• DOI: 10.1038/s42003-024-06502-0
• PMID: 39003419
• 文章类型: Journal Article
• 作者列表: Xu H,Wu Y,Chen Q,Yu Y,Meng Q,Qin N,Zhang W,Tao X,Li S,Tian T,Zhang L,Ma H,Cui J,Chu M

Mesh: Humans; Adenocarcinoma of Lung / genetics; China / epidemiology; East Asian People / genetics; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Genome-Wide Association Study; Lung Neoplasms / genetics; Polyadenylation; Polymorphism, Single Nucleotide; Quantitative Trait Loci

Abstract

Alternative polyadenylation (APA) plays a crucial role in cancer biology. Here, we used data from the 3\'aQTL-atlas, GTEx, and the China Nanjing Lung Cancer GWAS database to explore the association between apaQTL/eQTL-SNPs and the risk of lung adenocarcinoma (LUAD). The variant T allele of rs277646 in NIT2 is associated with an increased risk of LUAD (OR = 1.12, P = 0.015), lower PDUI values, and higher NIT2 expression. The 3\'RACE experiment showed multiple poly (A) sites in NIT2, with the rs277646-T allele causing preferential use of the proximal poly (A) site, resulting in a shorter 3\'UTR transcript. This leads to the loss of the hsa-miR-650 binding site, thereby affecting LUAD malignant phenotypes by regulating the expression level of NIT2. Our findings may provide new insights into understanding and exploring APA events in LUAD carcinogenesis.

摘要

选择性聚腺苷酸化（APA）在癌症生物学中起着至关重要的作用。这里,我们使用了来自3'aQTL-地图集的数据，GTEx,和中国南京肺癌GWAS数据库，以探讨apaQTL/eQTL-SNP与肺腺癌（LUAD）风险之间的关系。NIT2中rs277646的变异T等位基因与LUAD的风险增加相关(OR=1.12,P=0.015),较低的PDUI值，和更高的NIT2表达。3'RACE实验显示NIT2中有多个poly（A）位点，rs277646-T等位基因导致近端poly（A）位点的优先使用，导致较短的3UTR转录本。这导致hsa-miR-650结合位点的丢失，从而通过调控NIT2的表达水平影响LUAD的恶性表型。我们的发现可能为理解和探索LUAD癌变中的APA事件提供新的见解。