Crosstalk among Alternative Polyadenylation, Genetic Variants and Ubiquitin Modification Contribute to Lung Adenocarcinoma Risk

被引：0

作者：

Wu, Yutong ^{[1
]}

Yuan, Yanqiong ^{[1
]}

Xu, Huiwen ^{[1
]}

Zhang, Wendi ^{[1
]}

Ning, Anhui ^{[1
]}

Li, Siqi ^{[1
]}

Chen, Qiong ^{[1
]}

Tao, Xiaobo ^{[1
]}

Pan, Gongbu ^{[1
]}

Tian, Tian ^{[1
]}

Zhang, Lei ^{[1
]}

Chu, Minjie ^{[1
]}

Cui, Jiahua ^{[1
]}

机构：

[1] Nantong Univ, Sch Publ Hlth, Dept Epidemiol, Nantong 226019, Peoples R China

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2024年 / 25卷 / 15期

基金：

中国国家自然科学基金;

关键词：

lung adenocarcinoma; ubiquitination; alternative polyadenylation; susceptibility; CANCER; LIGASES; RNF213; LOCI;

D O I：

10.3390/ijms25158084

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：16

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