Nakamura Masato, Chiba Tetsuhiro, Kanayama Kengo, Kanzaki Hiroaki, Saito Tomoko, Kusakabe Yuko, Kato Naoya
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Hepatol Res. 2019 Jan;49(1):3-13. doi: 10.1111/hepr.13250. Epub 2018 Oct 19.
Due to the advances made in research based on next generation sequencers, it is now possible to detect and analyze epigenetic abnormalities associated with cancer. DNA methylation, various histone modifications, chromatin remodeling, and non-coding RNA-associated gene silencing are considered to be transcriptional regulatory mechanisms associated with gene expression changes. The breakdown of this precise regulatory system is involved in the transition to cancer. The important role of epigenetic regulation can be observed from the high rate of genetic mutations and abnormal gene expression leading to a breakdown in epigenetic gene expression regulation seen in hepatocellular carcinoma (HCC). Based on an understanding of epigenomic abnormalities associated with pathological conditions, these findings will lead the way to diagnosis and treatment. In particular, in addition to the fact that there are few choices in terms of extant drug therapies aimed at HCC, there are limits to their antitumor effects. The clinical application of epigenetic therapeutic agents for HCC has only just begun, and future developments are expected.
由于基于新一代测序仪的研究取得了进展，现在能够检测和分析与癌症相关的表观遗传异常。DNA甲基化、各种组蛋白修饰、染色质重塑以及与非编码RNA相关的基因沉默被认为是与基因表达变化相关的转录调控机制。这种精确调控系统的崩溃与癌症的转变有关。从肝细胞癌（HCC）中观察到的高基因突变率和导致表观遗传基因表达调控崩溃的异常基因表达中，可以看出表观遗传调控的重要作用。基于对与病理状况相关的表观基因组异常的理解，这些发现将为诊断和治疗指明方向。特别是，除了针对HCC的现有药物疗法选择很少之外，它们的抗肿瘤作用也有限。表观遗传治疗剂在HCC中的临床应用才刚刚开始，未来值得期待。
