摘要
肿瘤严重威胁人类健康,转录因子是肿瘤治疗的潜在靶点。作为重要的转录因子家族,E2F在细胞增殖与调控进程中发挥重要作用。然而,E2F家族转录因子在肿瘤发生进程中的表达规律、基因功能和分子互作等关键信息尚不清晰。基于此,本研究对TCGA数据库中我国10种高发肿瘤的转录组测序数据、突变数据和蛋白质互作数据进行整合分析,探究E2F家族转录因子的表达、结构、功能、突变和系统发生特征。结果显示,E2F家族转录因子中的E2F1和E2F7基因在多种肿瘤样本中规律性上调表达,参与调控细胞周期、细胞衰老等信号通路;其中,E2F1作为重要的调控因子与其他蛋白的相互作用最多。值得指出的是,E2F家族转录因子的基因突变类型在肿瘤类型和患者性别中均存在差异,基因扩增占比最大。系统发生分析显示,E2F家族转录因子的结构在包括果蝇、线虫和人类在内41个物种中保守,并且它们在物种演化过程中表现出基因扩张倾向。综上所述,本研究阐明了E2F家族转录因子在我国高发肿瘤中的表达规律、突变特征和演化规律,提示E2F家族转录因子是相关肿瘤疾病的新型分子诊断标志物,为抗肿瘤靶向药物研发提供理论依据。
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 E2F1 and E2F7 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.
作者
李飞飞
王韵
顾冀海
张玉明
柳峰松
倪志华
Feifei Li;Yun Wang;Jihai Gu;Yuming Zhang;Fengsong Liu;Zhihua Ni(School of Life Sciences,Hebei University,Baoding 071002,China;Key Laboratory of Zoological Systematics and Application of Hebei Province,Baoding 071002,China)
出处
《遗传》
CAS
CSCD
北大核心
2023年第7期580-592,共13页
Hereditas（Beijing)
基金
国家自然科学基金项目(编号:42207336)
河北省自然科学基金生物农业联合基金项目(编号:C202204227)
河北大学研究生创新项目(编号:HBU2022ss016)资助。
作者简介
李飞飞,在读硕士研究生,专业方向:生物化学与分子生物学,E-mail:huxiaoerfei@outlook.com;通讯作者:柳峰松,博士,教授,研究方向:分子免疫学,E-mail:liufengsong@hbu.edu.cn;通讯作者:倪志华,博士,副教授,研究方向:生物信息学、比较基因组学,E-mail:nizhihua@hbu.edu.cn。
