Du Gan, Yang Ruizhe, Qiu Jianguo, Xia Jie
Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China.
The First Clinical College, Chongqing Medical University, Chongqing, China.
J Clin Transl Hepatol. 2023 Feb 28;11(1):231-243. doi: 10.14218/JCTH.2022.00079. Epub 2022 Sep 13.
Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers and a leading cause of cancer-related mortality worldwide, but its pathogenesis remains largely unknown. Nevertheless, genomic instability has been recognized as one of the facilitating characteristics of cancer hallmarks that expedites the acquisition of genetic diversity. Genomic instability is associated with a greater tendency to accumulate DNA damage and tumor-specific DNA repair defects, which gives rise to gene mutations and chromosomal damage and causes oncogenic transformation and tumor progression. Histone deacetylases (HDACs) have been shown to impair a variety of cellular processes of genome stability, including the regulation of DNA damage and repair, reactive oxygen species generation and elimination, and progression to mitosis. In this review, we provide an overview of the role of HDAC in the different aspects of DNA repair and genome instability in HCC as well as the current progress on the development of HDAC-specific inhibitors as new cancer therapies.
肝细胞癌（HCC）是最常被诊断出的癌症之一，也是全球癌症相关死亡的主要原因，但其发病机制在很大程度上仍不清楚。然而，基因组不稳定性已被认为是癌症特征的促进特性之一，它加速了遗传多样性的获得。基因组不稳定性与积累DNA损伤和肿瘤特异性DNA修复缺陷的更大倾向相关，这会导致基因突变和染色体损伤，并引起致癌转化和肿瘤进展。组蛋白脱乙酰酶（HDACs）已被证明会损害基因组稳定性的多种细胞过程，包括DNA损伤和修复的调节、活性氧的产生和消除以及有丝分裂的进展。在本综述中，我们概述了HDAC在HCC中DNA修复和基因组不稳定性的不同方面所起的作用，以及HDAC特异性抑制剂作为新癌症治疗方法开发的当前进展。
