Gara Sudheer Kumar, Tyagi Monica Varun, Patel Dhaval Thakkur, Gaskins Kelli, Lack Justin, Liu Yi, Kebebew Electron
Thoracic Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
These authors contributed equally to this work & are first authors.
Oncotarget. 2020 Sep 8;11(36):3354-3370. doi: 10.18632/oncotarget.27703.
Recent evidence has implicated (Apolipoprotein B mRNA editing enzyme catalytic subunit 3B) as a source of mutations in breast, bladder, cervical, lung, head, and neck cancers. However, the role of APOBEC3B in adrenocortical carcinoma (ACC) and the mechanisms through which its expression is regulated in cancer are not fully understood. Here, we report that APOBEC3B is overexpressed in ACC and it regulates cell proliferation by inducing S phase arrest. We show high expression is associated with a higher copy number gain/loss at chromosome 4 and 8 and mutation rate in ACC. GATA3 was identified as a positive regulator of expression and directly binds the APOBEC3B promoter region. Both GATA3 and APOBEC3B expression levels were associated with patient survival. Our study provides novel insights into the function and regulation of APOBEC3B expression in addition to its known mutagenic ability.
最近的证据表明，载脂蛋白B信使核糖核酸编辑酶催化亚基3B（APOBEC3B）是乳腺癌、膀胱癌、宫颈癌、肺癌、头颈癌中基因突变的一个来源。然而，APOBEC3B在肾上腺皮质癌（ACC）中的作用以及其在癌症中表达调控的机制尚未完全明确。在此，我们报告APOBEC3B在ACC中过表达，并且它通过诱导S期阻滞来调节细胞增殖。我们发现高表达与ACC中4号和8号染色体上较高的拷贝数增加/缺失以及突变率相关。GATA3被鉴定为APOBEC3B表达的正调控因子，并且直接结合APOBEC3B启动子区域。GATA3和APOBEC3B的表达水平均与患者生存率相关。我们的研究除了揭示APOBEC3B已知的诱变能力外，还为其功能及表达调控提供了新的见解。
