Sadia Khulah, Castagna Annalisa, Udali Silvia, Ambrosani Francesca, Pattini Patrizia, Beri Ruggero, Argentino Giuseppe, Masutti Maria, Moruzzi Sara, Friso Simonetta
Department of Medicine, Section of Internal Medicine, University of Verona, Piazzale L.A. Scuro, 37134 Verona, Italy.
Cells. 2025 Aug 29;14(17):1337. doi: 10.3390/cells14171337.
Hepatocellular carcinoma (HCC) is a leading cause of global cancer-related mortality worldwide. Increasing evidence indicates that epigenetic mechanisms, which are potentially reversible and modifiable by environmental and nutritional factors, play a key role in hepatocarcinogenesis. Histone deacetylases (HDACs) are fundamental epigenetic modulators that regulate chromatin dynamics and ultimately gene transcription with important pathophysiological implications and promising therapeutic perspectives. The role of HDACs is gaining interest for the understanding of HCC development mechanisms and for the potential therapeutic implications of their natural and synthetic inhibitors. This review provides an overview on HDACs classification and their peculiar expression patterns in HCC, with a focus on zinc-dependent histone deacetylases (HDACs). HDAC inhibitors (HDACis), both synthetic and natural-derived compounds, are also discussed for their emerging effects in optimizing the anticancer efficacy of the current therapeutic strategies. Novel dietary-derived and bioactive compounds-based interventions are discussed in the context of HCC management as promising nutri-epigenetic avenues. Targeting HDACs bears a significant therapeutic potential for HCC management while further confirmatory clinical investigation is warranted.
肝细胞癌（HCC）是全球癌症相关死亡的主要原因。越来越多的证据表明，表观遗传机制在肝癌发生过程中起关键作用，这种机制可能会受到环境和营养因素的影响而发生逆转和改变。组蛋白脱乙酰酶（HDACs）是重要的表观遗传调节剂，可调节染色质动力学并最终影响基因转录，具有重要的病理生理学意义和广阔的治疗前景。HDACs在肝癌发生机制的理解以及其天然和合成抑制剂的潜在治疗意义方面正受到越来越多的关注。本综述概述了HDACs的分类及其在肝癌中的特殊表达模式，重点关注锌依赖性组蛋白脱乙酰酶（HDACs）。还讨论了HDAC抑制剂（HDACis），包括合成化合物和天然来源的化合物，它们在优化当前治疗策略的抗癌疗效方面的新作用。在肝癌管理的背景下，讨论了基于新型饮食来源和生物活性化合物的干预措施，这些措施有望成为营养表观遗传学的途径。靶向HDACs对肝癌管理具有显著的治疗潜力，但仍需进一步的临床研究予以证实。
