School of Life Sciences, Hebei University, Baoding 071002, China.
Key Laboratory of Zoological Systematics and Application of Hebei Province, Baoding 071002, China.
Yi Chuan. 2023 Jul 20;45(7):580-592. doi: 10.16288/j.yczz.23-029.
Tumors are serious threats to human health. The transcription factors are regarded as the potential targets for tumor treatment. As an important family of transcription factors, E2F family transcription factors (E2Fs) play vital roles in cell proliferation and regulation. However, the expression feature, gene functions, and molecular interactions of E2Fs in tumorigenesis are not clear. In this study, the transcriptome data, mutation data, and protein-protein interaction data of 10 high-incidence tumors in China from the TCGA database were integrated and analyzed to explore the expression, structure, function, mutation, and phylogenetic characteristics of E2Fs. The results showed that and were regularly upregulated in the tumor samples. Moreover, E2Fs participated in the regulation of the cell cycle, cell aging, and other signaling pathways. As an important regulator, E2F1 interacted with more proteins than other E2Fs. At the same time, the genetic mutation types of E2Fs varied in tumor type and patient sex, of which gene amplification accounts for the largest proportion. Phylogenetic analysis showed that E2Fs were conserved in 41 species, including fruit flies, nematodes, and humans. Meanwhile, E2Fs had a tendency for gene expansion during evolution. In conclusion, this study clarified the expression pattern, mutation characteristics, and evolutionary trend of E2Fs in high-incidence tumors in China, and suggested that E2F family transcription factors could be novel diagnostic markers for tumor diseases. Furthermore, this work can provide a theoretical basis for the development of anti-tumor-targeted drugs.
肿瘤是严重威胁人类健康的疾病。转录因子被认为是肿瘤治疗的潜在靶点。E2F 家族转录因子作为转录因子的重要家族之一，在细胞增殖和调控中发挥着重要作用。然而，E2F 在肿瘤发生中的表达特征、基因功能和分子相互作用尚不清楚。本研究整合分析了 TCGA 数据库中中国 10 种高发肿瘤的转录组数据、突变数据和蛋白质-蛋白质相互作用数据，探讨了 E2Fs 的表达、结构、功能、突变和系统发生特征。结果表明， 和 在肿瘤样本中呈规律性上调。此外，E2Fs 参与了细胞周期、细胞衰老等信号通路的调控。作为一个重要的调节因子，E2F1 与其他 E2Fs 相比，与更多的蛋白质相互作用。同时，E2Fs 的基因突变类型在肿瘤类型和患者性别上存在差异，其中基因扩增占比最大。系统发生分析表明，E2Fs 在包括果蝇、线虫和人类在内的 41 个物种中具有保守性。同时，E2Fs 在进化过程中存在基因扩张的趋势。综上所述，本研究阐明了中国高发肿瘤中 E2Fs 的表达模式、突变特征和进化趋势，提示 E2F 家族转录因子可作为肿瘤疾病的新型诊断标志物。此外，这项工作可为抗肿瘤靶向药物的开发提供理论基础。
