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乳酸修饰在癌症中的调控作用及治疗前景

Regulatory role and therapeutic prospect of lactate modification in cancer.

作者信息

Sun Mengdi, Wang Kejing, Lu Fang, Yu Donghua, Liu Shumin

机构信息

Graduate School, Heilongjiang University of Chinese Medicine, Harbin, China.

Institute of Traditional Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin, China.

出版信息

Front Pharmacol. 2025 Feb 17;16:1508552. doi: 10.3389/fphar.2025.1508552. eCollection 2025.

Abstract

Post-translational modifications (PTMs) of proteins refer to the process of adding chemical groups, sugars, or other molecules to specific residues of target proteins following their biosynthesis by ribosomes. PTMs play a crucial role in processes such as signal transduction, epigenetics, and disease development. Lactylation is a newly discovered PTM that, due to its close association with lactate-the end product of glycolytic metabolism-provides a new perspective on the connection between cellular metabolic reprogramming and epigenetic regulation. Studies have demonstrated that lactylation plays a significant role in tumor progression and is associated with poor clinical prognosis. Abnormal histone lactylation can influence gene expression in both tumor cells and immune cells, thereby regulating tumor progression and immunosuppression. Lactylation of non-histone proteins can also modulate processes such as tumor proliferation and drug resistance. This review summarizes the latest research progress in the field of lactylation, highlighting its roles and mechanisms in tumorigenesis, tumor development, the tumor microenvironment, and immunosuppression. It also explores the potential application value of lactylation in tumor-targeted therapy and combined immunotherapy.

摘要

蛋白质的翻译后修饰(PTMs)是指核糖体在目标蛋白质生物合成后,将化学基团、糖类或其他分子添加到目标蛋白质特定残基上的过程。翻译后修饰在信号转导、表观遗传学和疾病发展等过程中起着至关重要的作用。乳酰化是一种新发现的翻译后修饰,由于其与糖酵解代谢的终产物乳酸密切相关,为细胞代谢重编程与表观遗传调控之间的联系提供了新的视角。研究表明,乳酰化在肿瘤进展中起重要作用,且与不良临床预后相关。异常的组蛋白乳酰化可影响肿瘤细胞和免疫细胞中的基因表达,从而调节肿瘤进展和免疫抑制。非组蛋白的乳酰化也可调节肿瘤增殖和耐药性等过程。本综述总结了乳酰化领域的最新研究进展,重点介绍了其在肿瘤发生、肿瘤发展、肿瘤微环境和免疫抑制中的作用及机制。此外,还探讨了乳酰化在肿瘤靶向治疗和联合免疫治疗中的潜在应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2fb/11872897/dba0e7675106/fphar-16-1508552-g001.jpg

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