肿瘤缺氧微环境对DNA损伤应答过程的影响  

The effect of hypoxi microenvironment of tumor on DNA damage responses

作　　者：张涵威 孟祥宁[1] Zhang Hanwei;Meng Xiangning(Laboratory of Medical Genetics,Harbin Medical University;Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China(Harbin Medical University),Ministry of Education,Harbin 150081,China)

机构地区：[1]哈尔滨医科大学医学遗传学研究室,中国遗传资源保护与疾病防控教育部重点实验室(哈尔滨医科大学),150081

出　　处：《国际遗传学杂志》2020年第2期99-105,共7页International Journal of Genetics

基　　金：长江学者和创新团队发展计划资助(IRT1230)。

摘　　要：缺氧作为实体瘤微环境中的普遍特征,在肿瘤发生、进展、转移及治疗预后中发挥着关键作用。DNA损伤应答系统是维持基因组稳定性的高效修复机制,缺氧通过对DNA损伤应答过程的调节影响着基因组稳定性。本篇综述总结了缺氧对DNA损伤应答过程的多层面调控,包括改变细胞周期检查点激活方式及引发下游级联反应,下调DNA修复途径的转录和翻译过程,以及利用表观遗传学调控DNA损伤应答过程。这些对于理解肿瘤缺氧与DNA损伤应答、发现肿瘤潜在的治疗靶点、阻止肿瘤恶性进展具有重要意义。Hypoxia as a common feature in the microenvironment of solid tumors,plays a key role in the development,progression,metastasis and prognosis of tumors.The DNA damage response system is an efficient repair mechanism to maintain genomic stability.Hypoxia affects genomic stability by regulating the process of DNA damage responses.This review summarizes the multifacet regulation of hypoxia on DNA damage responses,including changes in cell cycle checkpoint activation and triggering of downstream cascade reactions,down-regulation of transcription and translation of DNA repair pathways,and epigenetic regulation of DNA damage responses.These are of great significance for understanding the response to hypoxia and DNA damage in tumors,discovering potential therapeutic targets of tumors,and preventing the malignant progression of tumors.

关 键 词：肿瘤 缺氧 DNA损伤应答 表观遗传学 

分 类 号：R730[医药卫生—肿瘤]