Abstract:
Zinc finger and BTB domain containing 20 (ZBTB20) is a key transcription repressor that regulates multiple physiological and pathophysiological processes. Thus far, the role of ZBTB20 in glioblastoma (GBM), a World Health Organization grade IV glioma, remains unclear. In the present study, the expression profile data of ZBTB20 in GBM tissues from public databases was analyzed. It was found that ZBTB20 expression in GBM tissues was significantly lower than that measured in lower grade glioma tissues. Furthermore, patients with GBM with lower ZBTB20 expression were associated with a shorter overall survival time. Gain- and loss-of-function experiments in GBM cells were also performed. The results demonstrated that ZBTB20 overexpression decreased GBM cell proliferation, while ZBTB20 knockdown significantly enhanced it. Cell cycle analysis showed the ZBTB20 overexpression may have inhibited proliferation through cell cycle arrest at the G2/M phase, while ZBTB20 knockdown increased the percentages of cells in both the S phase and G2/M phase. Ten-eleven translocation 1 (TET1) is an important tumor suppressor involved in the formation of various types of tumor, and it was upregulated in ZBTB20-overexpressing GBM cells. It was further demonstrated that ZBTB20 activated the TET1/FAS/caspase-3 pathway. The results of the present study therefore indicated the potential role of ZBTB20 as a tumor suppressor and therapeutic target for GBM.
摘要:
锌指和含BTB结构域20(ZBTB20)是调节多种生理和病理生理过程的关键转录阻遏物。到目前为止,ZBTB20在胶质母细胞瘤(GBM)中的作用,世界卫生组织四级神经胶质瘤,尚不清楚。在本研究中,分析了来自公共数据库的GBM组织中ZBTB20的表达谱数据。发现ZBTB20在GBM组织中的表达显著低于在低级别的神经胶质瘤组织中测得的表达。此外,ZBTB20表达较低的GBM患者的总体生存时间较短.还进行了GBM细胞中的功能增益和功能丧失实验。结果表明ZBTB20过表达降低了GBM细胞的增殖,而ZBTB20敲低则显著增强了它。细胞周期分析显示ZBTB20过表达可能通过细胞周期阻滞在G2/M期抑制增殖,而ZBTB20敲低增加了S期和G2/M期细胞的百分比。十十一易位1(TET1)是参与各类肿瘤形成的重要肿瘤抑制因子,并且它在ZBTB20过表达的GBM细胞中上调。进一步证明ZBTB20激活TET1/FAS/caspase-3途径。因此,本研究的结果表明ZBTB20作为GBM的肿瘤抑制剂和治疗靶标的潜在作用。