组蛋白乳酸化在消化系统肿瘤中的研究进展及展望

曾丹丹; 罗文凤; 叶甲舟; 林燕; 梁嵘

doi:10.19401/j.cnki.1007-3639.2025.04.011

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组蛋白乳酸化在消化系统肿瘤中的研究进展及展望

综述 | 更新时间：2025-12-31

- 组蛋白乳酸化在消化系统肿瘤中的研究进展及展望
- Research progress and prospect of histone lactylation in digestive system tumors
- 中国癌症杂志 2025年35卷第4期页码：424-430
- 作者机构：
  
  1. 广西医科大学附属肿瘤医院消化肿瘤内科，广西南宁 530000
  2. 广西医科大学附属肿瘤医院肝胆外科，广西南宁 530000
- 作者简介：
  
  [ "曾丹丹（ORCID: 0009-0002-6365-5760），硕士研究生在读。" ]
  梁嵘（ORCID: 0000-0003-0343-3277），博士，主任医师。
- 基金信息：
  
  国家自然科学基金项目(82060427);国家自然科学基金项目(82103297);广西医科大学杰出青年人才培养计划;广西医科大学高水平创新团队及杏湖学者计划;南宁市青秀区科技计划项目(2021007);南宁市青秀区科技计划项目(2021010);南宁市青秀区科技计划项目(2021012)
- DOI：10.19401/j.cnki.1007-3639.2025.04.011
  中图分类号：
- 收稿：2024-08-13，
  
  修回：2025-04-07，
  
  纸质出版：2025-04-30
- 稿件说明：
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曾丹丹, 罗文凤, 叶甲舟, 等. 组蛋白乳酸化在消化系统肿瘤中的研究进展及展望[J]. 中国癌症杂志, 2025,35(4):424-430.

Dandan ZENG, Wenfeng LUO, Jiazhou YE, et al. Research progress and prospect of histone lactylation in digestive system tumors[J]. China Oncology, 2025, 35(4): 424-430.
曾丹丹, 罗文凤, 叶甲舟, 等. 组蛋白乳酸化在消化系统肿瘤中的研究进展及展望[J]. 中国癌症杂志, 2025,35(4):424-430. DOI： 10.19401/j.cnki.1007-3639.2025.04.011.

Dandan ZENG, Wenfeng LUO, Jiazhou YE, et al. Research progress and prospect of histone lactylation in digestive system tumors[J]. China Oncology, 2025, 35(4): 424-430. DOI： 10.19401/j.cnki.1007-3639.2025.04.011.

摘要

组蛋白乳酸化修饰是一种新型的组蛋白翻译后修饰，通过乳酸分子与组蛋白赖氨酸残基的共价结合，在细胞代谢重编程中发挥关键作用，尤其在消化系统肿瘤的发生、发展中具有重要意义。近年来，组蛋白乳酸化在多种恶性肿瘤中的作用机制逐渐被揭示，显示其在肿瘤生物学中的广泛影响和临床潜力。本文重点梳理组蛋白乳酸化在消化系统肿瘤中的研究进展，具体分析其在胃癌、肝癌、结肠癌等主要消化道肿瘤中的作用机制。研究表明，乳酸化通过直接修饰组蛋白赖氨酸残基，调节肿瘤细胞的基因表达和染色质构象，进而促进肿瘤的增殖、侵袭和转移。乳酸化通过影响组蛋白与DNA的结合方式，改变染色质的开放性，增强癌基因的转录活性。此外，调控乳酸化水平或抑制乳酸化相关酶，如乳酸脱氢酶抑制剂、乳酸生成抑制剂及特定组蛋白乳酸化酶的靶向治疗，能够有效地抑制肿瘤的发生与发展，并在临床前模型中展示出潜在的治疗效果。本文从不同类型的消化道癌症出发，系统总结组蛋白乳酸化的作用机制，旨在为基于乳酸化修饰的靶向治疗策略提供新的研究方向和理论支持。

Abstract

Histone lactylation is a novel type of post-translational modification

where a lactate molecule covalently binds to the lysine residues of histones. This modification plays a key role in cellular metabolic reprogramming

particularly in digestive system tumorigenesis and progression. In recent years

the role of histone lactylation in various malignancies has been increasingly recognized

highlighting its broad impact on tumor biology and clinical potential. This article focused on the research progress of histone lactylation in digestive system cancers

specifically analyzing its mechanisms in major gastrointestinal cancers such as gastric cancer

liver cancer

and colon cancer. Studies have shown that lactylation modifies histone lysine residues directly

regulating tumor cell gene expression and chromatin conformation

thereby promoting tumor proliferation

invasion

and metastasis. Lactylation affects histone-DNA interactions

altering chromatin openness and enhancing the transcriptional activity of oncogenes. In addition

targeted therapies that modulate lactation levels or inhibit lactation-related enzymes

such as lactate dehydrogenase inhibitors

lactate production inhibitors

and specific histone lactonases

are effective in inhibiting tumorigenesis and progression and have demonstrated potential therapeutic efficacy in preclinical models. This article systematically summarized the mechanisms of histone lactylation in various types of gastrointestinal cancers

offering new research directions and theoretical support for targeted therapeutic strategies based on lactylation modification.

关键词

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references

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