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Abstract：
Ubiquitin modification and alternative polyadenylation play crucial roles in the onset and progression of cancer. Hence, this study aims to comprehensively and deeply understand gene regulation and associated biological processes in lung adenocarcinoma (LUAD) by integrating both mechanisms. Alternative polyadenylation (APA)-related E3 ubiquitin ligases in LUAD were identified through multiple databases, and the association between selected genetic loci influencing gene expression (apaQTL-SNPs) and LUAD risk were evaluated through the GWAS database of the Female Lung Cancer Consortium in Asia (FLCCA). Subsequently, the interaction between RNF213 and ZBTB20, as well as their functional mechanisms in LUAD, were investigated using bioinformatics analysis, Western blot, co-immunoprecipitation, and colony formation experiments. A total of five apaQTL-SNPs (rs41301932, rs4494603, rs9890400, rs56066320, and rs41301932), located on RNF213, were significantly associated with LUAD risk (p < 0.05), and they inhibit tumor growth through ubiquitin-mediated degradation of ZBTB20.
摘要：
泛素修饰和选择性聚腺苷酸化在癌症的发生和发展中起着至关重要的作用。因此，本研究旨在通过整合两者的机制，全面深入地了解肺腺癌（LUAD）的基因调控和相关生物学过程。通过多个数据库鉴定了LUAD中与多腺苷酸化（APA）相关的E3泛素连接酶，通过亚洲女性肺癌协会(FLCCA)的GWAS数据库评估了影响基因表达的选定遗传基因座(apaQTL-SNPs)与LUAD风险之间的关联.随后，RNF213和ZBTB20之间的相互作用，以及它们在LUAD中的功能机制，使用生物信息学分析进行了调查，蛋白质印迹,免疫共沉淀,和集落形成实验。共有五个apaQTL-SNP（rs41301932、rs4494603、rs9890400、rs56066320和rs41301932），位于RNF213上，与LUAD风险显着相关（p<0.05），它们通过泛素介导的ZBTB20降解抑制肿瘤生长。
