Fu Wenkang, Gao Long, Huang Chongfei, Yao Jia, Lin Yanyan, Bai Bing, Yue Ping, Liu Ying, Meng Wenbo, Qiao Liang, Li Xun
The First Clinical Medical School of Lanzhou University, Lanzhou, Gansu 730000, China.
Gansu Provincial Institute of Hepatopancreatobiliary, Lanzhou, Gansu 730000, China.
Discov Med. 2019 Jul;28(151):17-28.
Hepatobiliary cancers have poor prognosis due to their high level of invasiveness, distant metastasis, and chemotherapy resistance. Hepatocellular carcinoma is the most common type of hepatobiliary cancers representing the fourth leading cause of cancer death worldwide. There is an urgent need to identify the molecular drivers of hepatobiliary cancers to improve the therapeutic outcomes and patient prognosis. Histone modification is an important biological process that is critical in the regulation of epigenetic maintenance and modifications which in turn exert critical impacts on gene expression and chromatin structure stability. Histones may undergo a series of enzyme-catalyzed post-translational modifications such as acetylation, methylation, phosphorylation, ubiquitination, SUMOylating, crotonylation, and 2-hydroxyisobutyrylation. Dysregulation of histone-modifying enzyme may cause multiple diseases including cancers. As such, histone-modifying enzymes constitute a group of potential therapeutic targets. The aim of this review is to summarize the current understanding of the role of histone modification enzymes in regulating epigenetic alterations, cancer development, and their potential as therapeutic targets for hepatobiliary cancers.
肝胆癌因其高度侵袭性、远处转移和化疗耐药性而预后较差。肝细胞癌是最常见的肝胆癌类型，是全球癌症死亡的第四大主要原因。迫切需要确定肝胆癌的分子驱动因素，以改善治疗效果和患者预后。组蛋白修饰是一个重要的生物学过程，对表观遗传维持和修饰的调节至关重要，而表观遗传维持和修饰又对基因表达和染色质结构稳定性产生关键影响。组蛋白可能会经历一系列酶催化的翻译后修饰，如乙酰化、甲基化、磷酸化、泛素化、SUMO化、巴豆酰化和2-羟基异丁酰化。组蛋白修饰酶的失调可能导致包括癌症在内的多种疾病。因此，组蛋白修饰酶构成了一组潜在的治疗靶点。本综述的目的是总结目前对组蛋白修饰酶在调节表观遗传改变、癌症发展中的作用及其作为肝胆癌治疗靶点潜力的理解。
