Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Gene. 2019 Aug 30;711:143949. doi: 10.1016/j.gene.2019.143949. Epub 2019 Jun 28.
As a transcriptional repressor, Chromobox 8 (CBX8) overexpression is found to be associated with tumorigenesis in several cancers. However, its role in radiotherapy resistance remains poorly characterized. Our study is the first to explore the correlation between CBX8 and radioresistance. We report here that CBX8 is upregulated in Esophageal Squamous Cell Carcinoma (ESCC) tissues and cells and serves as an indicator of poor prognosis for ESCC patients. CBX8 knockdown inhibits cell proliferation, colony formation capability, DNA repair and promotes cell apoptosis. Moreover, the transcriptome sequencing analysis demonstrates that CBX8 downregulates the expression of Apoptotic protease activating factor 1 (APAF1), which is the core protein that mediates mitochondrial apoptotic pathways. APAF1 depletion could abrogate apoptosis induced by CBX8 knockdown in irradiated ESCC cells. Our results provide novel insight into CBX8 as a therapeutic target to improve the radiosensitivity of ESCC.
作为一种转录抑制因子，发现 Chromobox 8（CBX8）的过表达与多种癌症的肿瘤发生有关。然而，其在放射抵抗中的作用仍未得到充分描述。我们的研究首次探讨了 CBX8 与放射抵抗之间的相关性。我们在这里报告，CBX8 在食管鳞状细胞癌（ESCC）组织和细胞中上调，并作为 ESCC 患者预后不良的指标。CBX8 敲低抑制细胞增殖、集落形成能力、DNA 修复并促进细胞凋亡。此外，转录组测序分析表明，CBX8 下调凋亡蛋白酶激活因子 1（APAF1）的表达，APAF1 是介导线粒体凋亡途径的核心蛋白。在照射的 ESCC 细胞中，APAF1 耗竭可消除 CBX8 敲低诱导的细胞凋亡。我们的结果为 CBX8 作为提高 ESCC 放射敏感性的治疗靶点提供了新的见解。
