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载脂蛋白B编辑酶催化多肽样3A(APOBEC3A)在肿瘤发生中的功能及机制概述。

An overview of the functions and mechanisms of APOBEC3A in tumorigenesis.

作者信息

Yang Yuqi, Liu Nan, Gong Likun

机构信息

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

University of Chinese Academy of Sciences, Beijing 100049, China.

出版信息

Acta Pharm Sin B. 2024 Nov;14(11):4637-4648. doi: 10.1016/j.apsb.2024.08.020. Epub 2024 Aug 27.

Abstract

The APOBEC3 (A3) family plays a pivotal role in the immune system by performing DNA/RNA single-strand deamination. Cancers mostly arise from the accumulation of chronic mutations in somatic cells, and recent research has highlighted the A3 family as a major contributor to tumor-associated mutations, with A3A being a key driver gene leading to cancer-related mutations. A3A helps to defend the host against virus-induced tumors by editing the genome of cancer-associated viruses that invade the host. However, when it is abnormally expressed, it leads to persistent, chronic mutations in the genome, thereby fueling tumorigenesis. Notably, A3A is prominently expressed in innate immune cells, particularly macrophages, thereby affecting the functional state of tumor-infiltrating immune cells and tumor growth. Furthermore, the expression of A3A in tumor cells may directly affect their proliferation and migration. A growing body of research has unveiled that A3A is closely related to various cancers, which signifies the potential significance of A3A in cancer therapy. This paper mainly classifies and summarizes the evidence of the relationship between A3A and tumorigenesis based on the potential mechanisms, aiming to provide valuable references for further research on the functions of A3A and its development in the area of cancer therapy.

摘要

载脂蛋白B编辑酶催化多肽样蛋白3(APOBEC3,A3)家族通过进行DNA/RNA单链脱氨作用在免疫系统中发挥关键作用。癌症大多源于体细胞中慢性突变的积累,最近的研究突出了A3家族是肿瘤相关突变的主要促成因素,其中A3A是导致癌症相关突变的关键驱动基因。A3A通过编辑侵入宿主的癌症相关病毒的基因组,帮助宿主抵御病毒诱导的肿瘤。然而,当它异常表达时,会导致基因组中持续的慢性突变,从而促进肿瘤发生。值得注意的是,A3A在先天免疫细胞尤其是巨噬细胞中显著表达,从而影响肿瘤浸润免疫细胞的功能状态和肿瘤生长。此外,A3A在肿瘤细胞中的表达可能直接影响其增殖和迁移。越来越多的研究表明,A3A与多种癌症密切相关,这表明A3A在癌症治疗中具有潜在的重要意义。本文主要基于潜在机制对A3A与肿瘤发生关系的证据进行分类和总结,旨在为进一步研究A3A的功能及其在癌症治疗领域的发展提供有价值的参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70fd/11628810/9845b8d1d234/ga1.jpg

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