Wang Yan, Wu Zhisheng
Department of Neurology, First Hospital of Quanzhou, Quanzhou, China.
Front Oncol. 2021 Nov 11;11:761693. doi: 10.3389/fonc.2021.761693. eCollection 2021.
Glioma is the most common type of malignant tumor in the central nervous system with an unfavorable prognosis and limited treatment. In this study, we are devoted to addressing the prognostic value of DNA damage repair-related genes in low-grade glioma (LGG). We plotted the landscape of DNA damage repair (DDR)-related genes and identified SMC4 as an independent prognostic marker with integrated bioinformatics analysis, which is overexpressed in different histologic subtypes of glioma. We observed that SMC4 expression is elevated in recurrent LGG patients or those with advanced histologic staging. SMC4 depletion inhibits proliferation and induces increased replication damage in LGG cells. Lastly, we predicted and validated the transcription modulation of SMC4 by a transcription factor, MYB, at the -976bp~ -837bp of the SMC4 promoter region in LGG cells. Together, our study identified SMC4 as a potential prognostic biomarker for LGG patients, which functions to promote cell proliferation by repairing replication damage and the expression of SMC4 could be transcriptionally regulated by MYB.
胶质瘤是中枢神经系统最常见的恶性肿瘤类型，预后不佳且治疗有限。在本研究中，我们致力于探讨DNA损伤修复相关基因在低级别胶质瘤（LGG）中的预后价值。我们绘制了DNA损伤修复（DDR）相关基因图谱，并通过综合生物信息学分析确定SMC4为独立的预后标志物，其在不同组织学亚型的胶质瘤中均过表达。我们观察到，SMC4在复发性LGG患者或组织学分期较晚的患者中表达升高。SMC4缺失会抑制LGG细胞增殖并导致复制损伤增加。最后，我们预测并验证了转录因子MYB在LGG细胞中对SMC4启动子区域-976bp~ -837bp处的转录调控作用。总之，我们的研究确定SMC4是LGG患者潜在的预后生物标志物，它通过修复复制损伤促进细胞增殖，且SMC4的表达可受MYB转录调控。
