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20 November 2025

Non-Histone Lysine Modifications in Tumor Microenvironment: Mechanisms and Therapeutic Opportunities

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1
Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
2
School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
3
Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan 430022, China
4
Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
This article belongs to the Section Molecular Oncology

Abstract

Post-translational modifications (PTMs) on protein lysine residues, including lactylation, methylation, acetylation, ubiquitination, and succinylation, serve as critical regulators in tumorigenesis and progression. Histone PTMs participate in tumor development by modulating chromatin structure and regulating gene expression. Notably, accumulating evidence reveals that PTMs target extensive non-histone substrates. These modifications occurring on non-histone proteins also contribute to tumor-associated biological processes. In this review, we systematically summarize the impact of non-histone PTMs on tumor and the tumor immune microenvironment (TIME). Additionally, we discuss crosstalk between distinct PTMs, which complicates the regulatory mechanisms of protein function. An in-depth research on PTMs in tumors holds new insights for exploring promising clinical therapeutic strategies.

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