免疫原性微核的起源与生物医学意义  

The origin and biomedical implications of immunogenic micronucleus

作　　者：张城 汪旭[1] 郭锡汉[1] ZHANG Cheng;WANG Xu;GUO Xi-Han(Engineering Research Center for Sustainable Development and Utilization of Bioenergy,Ministry of Education,College of Life Sciences,Yunnan Normal University,Kunming 650500,China)

机构地区：[1]云南师范大学生命科学学院,生物能源持续开发与利用教育部工程研究中心,昆明650500

出　　处：《生命科学》2022年第4期392-400,共9页Chinese Bulletin of Life Sciences

基　　金：国家自然科学基金项目(31900410、31860301);云南省基础研究计划项目(202001AU070055、202101AT070112);云南师范大学优秀青年学者项目。

摘　　要：微核(micronuclei, MN)是独立于细胞核的小型类核结构,常见于肿瘤细胞。MN在结构和遗传活性方面表现出巨大异质性,相当部分的MN具有结构缺陷且倾向于破裂的核被膜(micronuclear envelope,mNE)。mNE破裂后,MN可启动染色体碎裂和固有免疫通路,暗示免疫原性MN (immunogenic MN, iMN)具有广泛的生物医学意义。该文首先讨论MN的起源、mNE易破裂的结构基础以及两个主要的分子和细胞模型,随后梳理出MN破裂后诱发染色体碎裂与激活cGAS-STING固有免疫通路的分子过程,最后总结了iMN在抗肿瘤活性和促肿瘤演化过程中所表现出的复杂作用及相应机制。iMN的研究为MN领域注入了全新的学术理论和思想。解析mNE不稳定的分子与结构基础以及iMN对肿瘤双向作用(iMN悖论)的机制将是未来几年细胞生物学和遗传学领域的研究热点之一。Micronuclei(MN) are small nucleus-like structures separated from the nucleus. MN are common in tumor cells and display a great heterogeneity in their structure and genetic activity. Due to the structural defects, micronuclear envelope(mNE) is rather prone to rupture, which triggers chromothripsis and innate immune responses. These findings suggest that immunogenic MN(iMN) has a wide range of biomedical implications. In this review, we firstly discuss the origin of MN, the structural basis of rupture-prone mNE, and two molecular and cellular models underlying mNE structural defects. Secondly, we explore the molecular mechanisms contributing to the induction of chromothripsis and activation of cGAS-STING innate immune pathway in ruptured MN. Finally, we summary the complicated roles and the corresponding mechanisms of iMN in suppressing tumor growth and promoting tumor evolution. As a new chapter in MN field, iMN has brought us new academic theories and ideas about MN. Dissecting the complexities of the molecular and structural origins of mNE instability, as well as the mechanisms for the dual roles of iMN in tumor(that is, iMN paradox), will be one of next frontiers in the fields of cell biology and genetics in the upcoming years.

关 键 词：核被膜 cGAS-STING通路 染色体碎裂 染色体外环状DNA 肿瘤 

分 类 号：Q24[生物学—细胞生物学] R392.1[医药卫生—免疫学]