Aiello Chiara, Felli Eric, Musarra Teresa, Nevi Lorenzo, Altomare Annamaria, Gracia-Sancho Jordi, Baiocchini Andrea, Carotti Simone
Microscopic and Ultrastructural Anatomy Research Unit, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy.
Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Int J Cancer. 2025 Nov 15;157(10):1991-2003. doi: 10.1002/ijc.70047. Epub 2025 Jul 22.
Abnormal epigenetic patterns are crucial for the progression of metabolic-associated steatotic liver disease (MASLD) and hepatocellular carcinoma (HCC) development. Recent research focused on the interplay between epigenetics and altered metabolic pathways in HCC from MASLD, suggesting that the reversibility of epigenetic changes offers potential for new therapeutic strategies. However, identifying effective epigenetic targets remains challenging due to the diverse etiologies of HCC. Targeting metabolic reprogramming, MASLD-associated HCC shows promise in reducing lipid anabolism. In this context, a more comprehensive understanding of metabolomic changes closely tied to druggable epigenetic modifications is of utmost importance. This review provides a concise summary of the key factors driving hepatocarcinogenesis in MASLD and delves deeper into the epigenetic mechanisms. Finally, we aim to present an overview of the primary mechanisms concerning the intricate bidirectional interplay between the metabolome and epigenetic modifications in MASLD-associated HCC, along with therapeutic strategies specifically targeting epigenetics and metabolomic alterations.
异常的表观遗传模式对于代谢相关脂肪性肝病（MASLD）的进展以及肝细胞癌（HCC）的发生发展至关重要。最近的研究聚焦于MASLD相关HCC中表观遗传学与代谢途径改变之间的相互作用，这表明表观遗传变化的可逆性为新的治疗策略提供了潜力。然而，由于HCC病因多样，确定有效的表观遗传靶点仍然具有挑战性。针对代谢重编程，MASLD相关HCC在减少脂质合成方面显示出前景。在此背景下，更全面地了解与可药物靶向的表观遗传修饰密切相关的代谢组学变化至关重要。本综述简要总结了驱动MASLD中肝癌发生的关键因素，并深入探讨了表观遗传机制。最后，我们旨在概述MASLD相关HCC中代谢组与表观遗传修饰之间复杂双向相互作用的主要机制，以及专门针对表观遗传学和代谢组学改变的治疗策略。
