癌症新型的诊疗靶点－APOBEC

APOBEC（“载脂蛋白质B mRNA编辑催化多肽”）是一类进化保守的胞苷脱氨酶家族。在人体内，已知含有保守的DNA胞嘧啶脱氨酶结构域的基因共有11种，包括AID、APOBEC1、APOBEC2、APOBEC3基因家族APOBEC3A、APOBEC3B、APOBEC3C、APOBEC3DE、APOBEC3F、APOBEC3G、APOBEC3H（分别称为A3A、A3B、A3C、A3D、A3F、A3G和A3H）和APOBEC4。APOBEC利用其脱氨酶活性通过与RNA和/或DNA结合，催化mRNA或使DNA中的胞嘧啶核苷酸转变为尿嘧啶，或者胞嘧啶核苷酸转变为胸腺嘧啶核苷酸，进而完成各自不同的功能。目前研究发现，AID及APOBEC3（A3s）的7种脱氨酶在人类的天然免疫和适应性免疫防御过程中发挥重要的作用，且在口腔癌，肺癌（腺癌和鳞状细胞癌），结直肠癌和乳腺癌等的诊疗过程中具有重要的潜在应用价值。AID可以通过将胞嘧啶脱氨基成尿嘧啶，来启动SHM (体细胞超突变)和CSR (类别转换重组)，进而在抗体多样性方面发挥作用。它的异常表达能够使B细胞淋巴瘤等恶性肿瘤的发病频率显著增加。而A3A、A3B通过胞嘧啶到尿嘧啶转换，以及自身表达量上调而在乳腺癌和肺癌诊疗中起作用。A3G通过APOBEC3G/miR 29/MMP2为了解结直肠癌肝转移和开发治疗晚期结肠癌的有效疗法开辟了新的途径。综上所述，本文将以AID，A3A，A3B，A3G为例子，对APOBEC在癌症诊断和治疗方面的应用进行综述，以期为进一步药物研究和临床应用等提供参考。

A Novel Diagnostic and Therapeutic Target for Cancers: APOBEC

APOBEC (apolipoprotein B mRNA editing catalyzed polypeptide) is an evolutionarily conserved cytosine deaminase family. There are 11 genes known to contain a conserved DNA cytosine deaminase domain in humans, including APOBEC3A，APOBEC3B，APOBEC3C，APOBEC3DE，APOBEC3F，APOBEC3G and APOBEC3H (A3A，A3B，A3C，A3D，A3F，A3G and A3H). It utilizes its deaminase activity to catalyze the transfer of cytosine to uracil nucleotides in mRNA or DNA by binding to RNA or DNA to elicit different functions. The current study found that AID and APOBEC3 (A3s) play an important role in human natural immune and adaptive immune defense processes. It has important potential applications in the diagnosis and treatment of oral cancer, lung cancer (adenocarcinoma and squamous cell carcinoma), colorectal cancer and breast cancer. AID can initiate somatic hypermutation (SHM) and category transformation recombination (CSR) by deamination of cytosine into uracil to play a role in antibody diversity, and its abnormal expression can significantly increase the frequency of malignant tumors such as B-cell lymphoma. In this paper, we review the application of APOBEC in diagnostic and therapeutic of cancer, which hopefully will provide a reference for further drug development and clinical research. A3A and A3B play roles in the diagnosis and treatment of breast cancer and lung cancer through cytosine to uracil conversion and up-regulation of self-expression. A3G opens a new way for understanding colorectal cancer liver metastasis and developing effective therapies for advanced colon cancer through APOBEC3G/miR-29/MMP2. In this paper, we will use AID, A3A, A3B, A3G as an example to review the applications of APOBEC in diagnostic and therapeutic of cancer, which hopefully will provide a reference for further drug development and clinical research.