Xia Jin-Kun, Qin Xue-Qian, Zhang Lu, Liu Shu-Jun, Shi Xiao-Lei, Ren Hao-Zhen
Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Hepatobiliary Institute Nanjing University, Nanjing, China.
Front Genet. 2022 Aug 25;13:982222. doi: 10.3389/fgene.2022.982222. eCollection 2022.
Hepatocellular Carcinoma (HCC) is the most frequent malignant tumor of the liver, but its prognosis is poor. Histone acetylation is an important epigenetic regulatory mode that modulates chromatin structure and transcriptional status to control gene expression in eukaryotic cells. Generally, histone acetylation and deacetylation processes are controlled by the opposing activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). Dysregulation of histone modification is reported to drive aberrant transcriptional programmes that facilitate liver cancer onset and progression. Emerging studies have demonstrated that several HDAC inhibitors exert tumor-suppressive properties via activation of various cell death molecular pathways in HCC. However, the complexity involved in the epigenetic transcription modifications and non-epigenetic cellular signaling processes limit their potential clinical applications. This review brings an in-depth view of the oncogenic mechanisms reported to be related to aberrant HCC-associated histone acetylation, which might provide new insights into the effective therapeutic strategies to prevent and treat HCC.
肝细胞癌（HCC）是肝脏最常见的恶性肿瘤，但其预后较差。组蛋白乙酰化是一种重要的表观遗传调控方式，可调节染色质结构和转录状态，以控制真核细胞中的基因表达。一般来说，组蛋白乙酰化和去乙酰化过程由组蛋白乙酰转移酶（HATs）和组蛋白去乙酰化酶（HDACs）的相反活性控制。据报道，组蛋白修饰失调会驱动异常的转录程序，促进肝癌的发生和发展。新兴研究表明，几种HDAC抑制剂通过激活HCC中的各种细胞死亡分子途径发挥肿瘤抑制特性。然而，表观遗传转录修饰和非表观遗传细胞信号传导过程中涉及的复杂性限制了它们的潜在临床应用。本综述深入探讨了据报道与异常HCC相关组蛋白乙酰化有关的致癌机制，这可能为预防和治疗HCC的有效治疗策略提供新的见解。
