Epigenetic and post-translational modifications in ferroptosis regulation and hepatocellular carcinoma: New frontiers in therapeutic targeting

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice Pub Date : 2025-04-22 DOI:10.1016/j.prp.2025.155991

Soheil Bolandi , Samaneh Dodge , Zahra Zahed , Anvar Soleimani , Khaterehsadat Monirvaghefi , Mahshid Ghodsifar , Moein Ghasemi , Nahal Aghajamal avval , Seyedeh Sahar Mojtaba Zadeh , Seyed Mohammad Ali Fazayel , Reza Morovatshoar , Vahid Barfi , Qumars Behfar , Sima Dehghani

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引用次数: 0

Abstract

Hepatocellular carcinoma (HCC), the predominant kind of liver cancer, continues to be a significant contributor to cancer-related deaths globally, influenced by intricate molecular processes and strong resistance to existing chemotherapy. Iron-dependent lipid peroxidation induces ferroptosis, a controlled form of cell death that plays a crucial role in inhibiting tumor growth and treatment resistance in HCC. Recent research has shown that epigenetic modifications, such as DNA methylation, histone modifications, regulation by non-coding RNAs (ncRNAs), and post-translational modification (PTM) like ubiquitination, phosphorylation, acetylation, and methylation, play a crucial role in fine-tuning ferroptosis. These alterations alter the structure of chromatin, gene expression, and protein function, thereby affecting cancer cells' fate. This review emphasizes the complex functions of epigenetic and post-translational alterations in controlling ferroptosis, providing valuable insights into their potential as therapeutic targets in HCC. The unraveling of these pathways offers a significant opportunity for novel therapies targeted at surmounting drug resistance and enhancing patient outcomes in liver cancer.

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铁下垂调节和肝细胞癌的表观遗传和翻译后修饰：治疗靶向的新领域

肝细胞癌（HCC）是主要的肝癌类型，受复杂的分子过程和对现有化疗的强烈耐药性的影响，仍然是全球癌症相关死亡的重要原因。铁依赖性脂质过氧化诱导铁凋亡，这是一种受控的细胞死亡形式，在抑制肝癌肿瘤生长和治疗抵抗中起着至关重要的作用。最近的研究表明，表观遗传修饰，如DNA甲基化、组蛋白修饰、非编码rna （ncRNAs）的调控，以及泛素化、磷酸化、乙酰化和甲基化等翻译后修饰（PTM），在铁死亡的微调中起着至关重要的作用。这些改变改变了染色质结构、基因表达和蛋白质功能，从而影响了癌细胞的命运。这篇综述强调了表观遗传和翻译后改变在控制铁下垂中的复杂功能，为它们作为HCC治疗靶点的潜力提供了有价值的见解。这些途径的揭示为针对克服耐药性和提高肝癌患者预后的新疗法提供了重要的机会。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pathology, research and practice 医学-病理学

CiteScore

5.00

自引率

3.60%

发文量

405

审稿时长

24 days

期刊介绍： Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.