E2F1-driven EXOSC10 transcription promotes hepatocellular carcinoma growth and stemness: a potential therapeutic target.

IF 2.5 3区生物学

Hereditas Pub Date : 2025-04-12 DOI:10.1186/s41065-025-00430-7

Haoyue Deng, Dingyong Wu, Yongpeng He, Xiaolei Yu, Jifei Liu, Yanrui Zhang, Bing Leng, Xiaofeng Yuan, Liguo Xiao

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引用次数: 0

Abstract

Background: E2F Transcription Factor 1 (E2F1) is a transcription factor that plays a crucial role in the growth of many cancers, including hepatocellular carcinoma (HCC). Herein, this study probed the functions and underlying mechanisms of E2F1 in HCC tumorigenesis.

Methods: The expression profiles of E2F1 and Exosome Component 10 (EXOSC10) were detected using qRT-PCR and western blotting. Functional experiments were carried out using 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, tube formation, and sphere formation assays in vitro, as well as xenograft experiments in vivo, respectively. Stemness-related proteins were assayed using western blotting. The interaction between E2F1 and EXOSC10 was verified using bioinformatics analysis and dual-luciferase reporter assay.

Results: E2F1 was highly expressed in HCC tissues and cells, and was associated with advanced TNM stage, distant metastasis, and short survival rate. Functionally, knockdown of E2F1 suppressed HCC cell proliferation, angiogenesis, and stemness, and induced cell apoptosis. Mechanistically, E2F1 directly bound to the promoter region of EXOSC10 to up-regulate its expression. EXOSC10 silencing impaired HCC cell proliferation, angiogenesis, and stemness. Moreover, the anticancer effects of E2F1 knockdown were reversed by EXOSC10 elevation. In vivo assay, E2F1 deficiency suppressed HCC tumor growth and eliminated cancer stemness, while these effects were abolished by EXOSC10 up-regulation.

Conclusion: E2F1 promotes EXOSC10 transcription and then facilitates HCC growth and cancer stemness, revealing a potential target for HCC therapy.

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e2f1驱动的EXOSC10转录促进肝细胞癌的生长和干细胞：一个潜在的治疗靶点。

背景：E2F转录因子1 （E2F1）是一种转录因子，在包括肝细胞癌（HCC）在内的许多癌症的生长中起着至关重要的作用。本研究探讨了E2F1在HCC肿瘤发生中的作用及其机制。方法：采用qRT-PCR和western blotting检测E2F1和Exosome Component 10 （EXOSC10）的表达谱。分别采用5-乙基-2′-脱氧尿苷（EdU）、流式细胞术、体外成管和成球实验以及体内异种移植实验进行功能实验。用western blotting检测干细胞相关蛋白。利用生物信息学分析和双荧光素酶报告试验验证了E2F1和EXOSC10之间的相互作用。结果：E2F1在HCC组织和细胞中高表达，与TNM晚期、远处转移、短生存率相关。在功能上，E2F1基因的下调抑制了肝癌细胞的增殖、血管生成和干细胞形成，并诱导细胞凋亡。机制上，E2F1直接结合到EXOSC10的启动子区域上调其表达。EXOSC10沉默会损害HCC细胞的增殖、血管生成和干细胞性。此外，E2F1敲低的抗癌作用被EXOSC10升高逆转。在体内实验中，缺乏E2F1抑制HCC肿瘤生长并消除癌干性，而这些作用通过上调EXOSC10而被消除。结论：E2F1促进EXOSC10转录，进而促进HCC生长和癌变，揭示了HCC治疗的潜在靶点。

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来源期刊

Hereditas Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.80

自引率

3.70%

发文量

期刊介绍： For almost a century, Hereditas has published original cutting-edge research and reviews. As the Official journal of the Mendelian Society of Lund, the journal welcomes research from across all areas of genetics and genomics. Topics of interest include human and medical genetics, animal and plant genetics, microbial genetics, agriculture and bioinformatics.