Bueloni Barbara, Garcia Fernandez de Barrena Maite, Avila Matias Antonio, Bayo Juan, Mazzolini Guillermo
Hepatology and Gene Therapy Program, Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral, Pilar, Argentina.
HZ4 Liver Inc./Spectrum, Dover, Delaware, USA.
eGastroenterology. 2025 May 4;3(2):e100186. doi: 10.1136/egastro-2025-100186. eCollection 2025.
Hepatocellular carcinoma (HCC) typically develops in the context of chronic liver disease, where prolonged hepatocyte exposure to inflammation drives the synergistic accumulation of genetic and epigenetic alterations. Epigenetic regulation encompasses multiple mechanisms that govern the transcription machinery accessibility to DNA. This process is regulated by the addition and removal of covalent marks on chromatin, which can either affect DNA-histone interactions or serve as scaffolds for other proteins, among other mechanisms. Recent research has revealed that epigenetic alterations can disrupt chromatin homeostasis, redirecting transcriptional regulation to favour cancer-promoting states. Consequently, these alterations play a pivotal role in the acquisition of cancer hallmarks and provide insights into several biological processes involved in hepatocarcinogenesis. This review highlights the key epigenetic mechanisms underlying the development, progression and dissemination of HCC, with a particular focus on DNA methylation and histone post-translational modifications. This knowledge is relevant for guiding the development of innovative therapeutic approaches based on epigenetic modulators.
肝细胞癌（HCC）通常在慢性肝病的背景下发生，长期暴露于炎症环境中的肝细胞会促使基因和表观遗传改变协同积累。表观遗传调控包括多种机制，这些机制控制着转录机器对DNA的可及性。这个过程由染色质上共价标记的添加和去除来调节，这可以影响DNA与组蛋白的相互作用，或者作为其他蛋白质的支架，以及其他机制。最近的研究表明，表观遗传改变会破坏染色质稳态，将转录调控重定向为有利于癌症促进状态。因此，这些改变在癌症特征的获得中起着关键作用，并为肝癌发生过程中涉及的几个生物学过程提供了见解。本综述重点介绍了HCC发生、发展和转移的关键表观遗传机制，特别关注DNA甲基化和组蛋白翻译后修饰。这些知识对于指导基于表观遗传调节剂的创新治疗方法的开发具有重要意义。
