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全基因组功能整合确定了在肝细胞癌中MAZ控制的RPS14失调

Linyu Han¹, Yanfei Huo¹, Linying Huang¹

¹Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong Province, China.

Archives of toxicology

|January 8, 2024

概括

遗传因素影响B型肝炎病毒 (HBV) 相关的肝癌 (HCC) 风险. 一项新的研究确定了RPS14基因中的特定遗传变异 (SNP rs13170300),该变异影响HCC发育.

科学领域:

基因组学就是基因组学.
肝病学肝病学是一种肝病学.
癌症生物学癌症生物学

背景情况:

慢性乙型肝炎病毒 (HBV) 感染是肝细胞癌 (HCC) 的主要危险因素,特别是在东亚.
遗传倾向对HCC的发展起着作用,因为只有少数感染HBV的个体会患上这种疾病.
现有的全基因组关联研究 (GWAS) 已经确定了与HBV相关的HCC相关的SNP,但功能机制在很大程度上仍然未知.

研究的目的:

开发一种整合功能基因组学方法 (TUIFGA),以确定与HBV相关的HCC的因果遗传多态性.
调查已识别的单核酸多态 (SNPs) 对基因调节和HCC风险的功能影响.
阐明RPS14在HBV相关HCC的发病过程中的作用.

主要方法:

开发了更新的整合功能基因组学方法 (TUIFGA),结合了TF基因组学,ATAC-seq,DNAase-seq和1000个基因组项目数据.
在RPS14促进体中的MAZ转录因子结合基因内识别了SNP rs13170300.
在两个独立的病例控制组中验证了rs13170300与HCC风险的关联,并分析了它对MAZ结合和RPS14基因表达的影响.

主要成果:

发现SNP rs13170300与HBV相关的HCC风险显著相关,T等位基因赋予保护.
证明rs13170300改变了MAZ与RPS14促进体结合,导致RPS14表达的等位基因特异性变化.
确立了RPS14作为HCC中激活AKT信号通路的新瘤基因.

结论:

已识别的SNP rs13170300为与HBV相关的HCC的遗传基础提供了功能性见解.
通过调节AKT信号通路,RPS14在HCC中充当瘤基因.
这些发现可能会为个性化癌症预防策略和治疗HBV相关HCC的开发提供信息.

关键词:

遗传的多态化遗传多态化肝细胞癌是肝细胞癌.这是一个迷宫,一个迷宫.预测预后预测预测在RPS14中使用RPS14.

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