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APOBECs家族成员在癌症进化发育过程中的核心作用
刘文斌1,邓阳2,于浩义3,曹广文1*
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(1. 第二军医大学热带医学与公共卫生学系流行病学教研室, 上海 200433;
2. 泰山医学院流行病学研究所, 泰安 271000;
3. 第二军医大学学员旅学员5队, 上海 200433
*通信作者)
摘要:
癌症形成于促炎症状态的微环境之中, 遵循着“变异-选择-适应”的达尔文进化规律。这一过程的遗传学基础是体细胞突变的产生与积累。目前, 大量体细胞突变的产生机制以及环境压力下变异细胞的自然选择过程尚不明确。载脂蛋白B mRNA编辑酶催化多肽 (apolioprotein B mRNA-editing enzyme catalytic polypeptide, APOBEC) 家族是一类高效的胞苷脱氨酶, 其转录可被促炎症细胞因子和趋化因子激活, 并在人体的固有和获得性免疫机制中发挥重要作用。APOBECs家族在抑制病毒复制的同时, 也驱使有促癌作用的病毒突变体形成;其基因编码功能还可以诱发有促癌作用的驱动突变产生。作为在炎-癌转化中发挥桥梁作用的标志性酶, APOBECs家族对癌症的进化发育至关重要。
关键词:  胞苷脱氨酶  变异  肿瘤  进化
DOI:10.3724/SP.J.1008.2014.01304
投稿时间:2014-09-23修订日期:2014-10-30
基金项目:国家重点基础研究发展计划(“973”计划, 2015CB554000).
Apolioprotein B mRNA-editing enzyme catalytic polypeptide family plays a central role in cancer evolution
LIU Wen-bin1,DENG Yang2,YU Hao-yi3,CAO Guang-wen1*
(1. Department of Epidemiology, Faculty of Tropical Medicine and Public Health, Second Military Medical University, Shanghai 200433, China;
2. Institute of Epidemiology, Taishan Medical College, Taian 271000, Shandong, China;
3. The 5th Student Brigade, Second Military Medical University, Shanghai 200433, China
*Corresponding author)
Abstract:
The process of carcinogenesis starts in the proinflammatory microenvironment and is abided by Darwinian evolution theory: mutation-selection-adaption; and the genetic basis of this process is the generation and accumulation of somatic mutations. Currently the molecular mechanisms of massive nucleotide alterations and natural selection of mutant cells under environment pressure still remain unclear. The apolioprotein B mRNA-editing enzyme catalytic polypeptide (APOBEC) family of cytidine deaminases, which is transcriptionally induced by proinflammatory cytokine and chemokine, plays important roles in the innate and adaptive immunities of human organism. APOBECs can not only inhibit viral replication but also facilitate the generation of cancer-promoting viral mutants; they can also facilitate the generation of driver mutations in the host genes, thus contribute to the development of cancers. APOBECs, as hallmark enzymes bridging inflammation and cancer, play an important role in cancer evolution.
Key words:  cytidine deaminase  mutation  neoplasms  evolution