a Department of Surgery, Faculty of Medicine , The Chinese University of Hong Kong, Prince of Wales Hospital , Hong Kong , China.
b Department of Otorhinolaryngology , The Chinese University of Hong Kong, Prince of Wales Hospital , Hong Kong , China.
Expert Opin Ther Targets. 2018 Oct;22(10):817-822. doi: 10.1080/14728222.2018.1516753. Epub 2018 Sep 6.
Zinc-binding protein-89 (ZBP-89) is a Krüppel-type zinc-finger transcription factor that regulates target gene expression profiles via directly binding to GC-rich gene promoters, recruiting chromatin modifiers or by interacting with other proteins. The importance of ZBP-89 in the regulation of cell cycle arrest and apoptosis has led to increased interest and investigations for its role in cancer development. Areas covered: We describe ZBP-89 as a candidate therapeutic target for hepatocellular carcinoma (HCC) from several perspectives. ZBP-89 can upregulate apoptosis in HCC in a p53-dependent or - independent manner. In addition, the negative regulation of ZBP-89 on liver cancer stemness sheds light on its possible effect on sensitizing HCC to chemotherapies and the reduction of HCC relapse. The prognostic significance of ZBP-89 in HCC patients further suggests its clinical importance as a potential tumor suppressor. Expert opinion: Given the roles of ZBP-89 in HCC, we believe, ZBP-89 is a promising therapeutic target for enhancing apoptosis and diminishing the liver cancer stemness. At the same time, we also face a series of challenges, especially in the clinical implication of ZBP-89. Resolving the current controversies will advance the development of ZBP-89 for anti-HCC therapy.
锌结合蛋白-89(ZBP-89)是一种 Krüppel 型锌指转录因子,通过直接结合富含 GC 的基因启动子、招募染色质修饰物或与其他蛋白相互作用,调节靶基因表达谱。ZBP-89 在细胞周期阻滞和细胞凋亡中的重要性使其在癌症发生中的作用引起了越来越多的关注和研究。
我们从几个角度将 ZBP-89 描述为肝细胞癌(HCC)的候选治疗靶点。ZBP-89 可以依赖或不依赖 p53 上调 HCC 中的细胞凋亡。此外,ZBP-89 对肝癌干细胞的负调控提示其可能对增敏 HCC 化疗和减少 HCC 复发有影响。ZBP-89 在 HCC 患者中的预后意义进一步表明其作为潜在肿瘤抑制因子的临床重要性。
鉴于 ZBP-89 在 HCC 中的作用,我们认为 ZBP-89 是增强细胞凋亡和减少肝癌干细胞特性的有前途的治疗靶点。同时,我们也面临着一系列挑战,特别是在 ZBP-89 的临床意义方面。解决当前的争议将推动 ZBP-89 用于抗 HCC 治疗的发展。