E2F8 is a Potential Therapeutic Target for Hepatocellular Carcinoma.
E2F8 is a Potential Therapeutic Target for Hepatocellular Carcinoma.
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DOI：
10.7150/jca.18255
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发表时间：
2017
影响因子：
3.9
通讯作者：
Xing F
中科院分区：
文献类型：
--
作者：
Lv Y;Xiao J;Liu J;Xing F
E2F转录因子在多种组织和器官中广泛表达，具有多种与细胞增殖、分化、DNA修复、细胞周期和细胞凋亡相关的调节功能。E2F8是新近发现的E2F家族成员，具有与E2F1-6不同的重复DNA结合域特征，以二聚化伙伴非依赖的方式控制基因表达。它对血管生成、淋巴管生成和胚胎发育都是不可或缺的。虽然E2F8和E2F7在许多细胞代谢中具有互补和重叠的功能，但在肝细胞癌中，E2F8而不是E2F7过表达，通过激活E2F1/Cyclin D1信号通路调节细胞周期从G1期到S期的转变或在转录上抑制CDK1诱导肝细胞多倍化，从而促进肝癌的发生发展。它还涉及多种细胞生理功能和病理过程，可能为某些疾病的治疗带来新的突破，尤其是肝细胞癌。现就E2F8的相关功能、作用机制及应用前景等方面的最新进展进行综述。
E2F transcriptional factors are widely expressed in a number of tissues and organs, possessing many regulatory functions related to cellular proliferation, differentiation, DNA repair, cell-cycle and cell apoptosis. E2F8 is a recently identified member of the E2F family with a duplicated DNA-binding domain feature discriminated from E2F1-6, controlling gene expression in a dimerization partner-independent manner. It is indispensable for angiogenesis, lymphangiogenesis and embryonic development. Although E2F8 and E2F7 perform complementary and overlapping functions in many cell metabolisms, E2F8, but not E2F7, overexpresses remarkably in hepatocellular carcinoma (HCC) to facilitate the HCC occurrence and development via activating a E2F1/ Cyclin D1 signaling pathway to regulate the G1- to S-phase transition of cell cycle progression or transcriptionally suppressing CDK1 to induce hepatocyte polyploidization. It also involves closely a variety of cellular physiological functions and pathological processes, which may bring a new breakthrough for the treatment of certain diseases, especially the HCC. Here, we summarize the latest progress of E2F8 on its relevant functions and mechanisms as well as potential application.