Department of Medical Genetics and Developmental Biology, School of Medicine, The Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Southeast University, Nanjing, 210009, China.
School of Life Science and Technology, Southeast University, Nanjing, China.
Sci Rep. 2024 Nov 29;14(1):29695. doi: 10.1038/s41598-024-81642-1.
ETS variant transcription factor 5 (ETV5), a master transcription factor during development, exerts vital function on the occurrence and progression of various cancers. In order to systematically analyze and explore ETV5 potential specific regulatory mechanisms in pan-cancer, RNA sequencing data and clinicopathological features of patients with various tumors were obtained through the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, and an integrated data mining analysis was carried out, including the association of ETV5 expression with patient prognosis, drug sensitivity and epigenetic modification. The results revealed that abnormally highly expressed ETV5 resulted in unfavorable prognosis and differential drug sensitivity in multiple malignancies, and its expression was associated with epigenetic modification modulators including EZH2. ETV5 related genes were enriched in tumorigenesis biological processes and signaling pathways. In hepatocellular carcinoma, ETV5 expression was correlated with patients' tumor pathological stage and resulted in adverse outcome of patients. Our further experiments evidences indicated that ETV5 facilitated cell proliferation and reduced sensitivity to GSK126 via regulating EZH2. Collectively, this study comprehensively elucidates the carcinogenic effects and molecular mechanisms of ETV5 in tumorigenesis and development, and provides theoretical basis and guidance for tumor diagnosis, targeted therapy for ETV5 and clinical epigenetic drug research.
ETS 变体转录因子 5(ETV5)是发育过程中的主要转录因子,对各种癌症的发生和发展起着至关重要的作用。为了系统地分析和探讨 ETV5 在泛癌中潜在的特异性调控机制,我们通过癌症基因组图谱(TCGA)和基因型组织表达(GTEx)数据库获得了患者各种肿瘤的 RNA 测序数据和临床病理特征,并进行了综合数据挖掘分析,包括 ETV5 表达与患者预后、药物敏感性和表观遗传修饰的相关性。结果表明,异常高表达的 ETV5 导致多种恶性肿瘤的预后不良和药物敏感性差异,其表达与包括 EZH2 在内的表观遗传修饰调节剂有关。ETV5 相关基因在肿瘤发生的生物学过程和信号通路中富集。在肝细胞癌中,ETV5 的表达与患者的肿瘤病理分期相关,导致患者的不良预后。我们的进一步实验证据表明,ETV5 通过调节 EZH2 促进细胞增殖并降低对 GSK126 的敏感性。总之,本研究全面阐明了 ETV5 在肿瘤发生和发展中的致癌作用和分子机制,为肿瘤诊断、ETV5 的靶向治疗和临床表观遗传药物研究提供了理论依据和指导。