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Background: The complexity of cancer is intricately linked to its multifaceted biological processes, including the roles of the tumor microenvironment (TME) as well as genetic and metabolic regulation. Histone lactylation has recently emerged as a novel epigenetic modification mechanism that plays a pivotal role in regulating cancer initiation, proliferation, invasion, and metastasis.
Objective: This review aims to elucidate the role of histone lactylation in modulating various aspects of tumor biology, including DNA repair mechanisms, glycolytic metabolic abnormalities, functions of non-tumor cells in the TME, and the promotion of tumor inflammatory responses and immune escape. Additionally, the review explores potential therapeutic strategies targeting histone lactylation.
Methods: A comprehensive literature review was performed, analyzing recent findings on histone lactylation and its impact on cancer biology. This involved a systematic examination of studies focusing on biochemical pathways, cellular interactions, and clinical implications related to histone lactylation.
Results: Histone lactylation was identified as a critical regulator of tumor cell DNA repair mechanisms and glycolytic metabolic abnormalities. It also significantly influences the functions of non-tumor cells within the TME, promoting tumor inflammatory responses and immune escape. Moreover, histone lactylation acts as a multifunctional biological signaling molecule impacting immune responses within the TME. Various cell types within the TME, including T cells and macrophages, were found to regulate tumor growth and immune escape mechanisms through lactylation.
Conclusion: Histone lactylation offers a novel perspective on tumor metabolism and its role in cancer development. It presents promising opportunities for the development of innovative cancer therapies. This review underscores the potential of histone lactylation as a therapeutic target, paving the way for new strategies in cancer treatment.
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http://dx.doi.org/10.1007/s13258-024-01554-2 | DOI Listing |
Front Endocrinol (Lausanne)
September 2025
Department of Orthopedics I, Second Affiliated Hospital, Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China.
Background: Emerging evidence indicates that lactase-mediated histone lactylation can activate osteogenic gene expression and promote bone formation. However, the role of lactylation-related genes (LRGs) in osteoporosis (OP) remains unclear. This study aims to clarify the key roles of LRGs and the molecular mechanisms of related biomarkers in OP.
View Article and Find Full Text PDFFree Radic Biol Med
September 2025
Department of General Surgery, Jiangnan University Medical Center, Wuxi, PR China. Electronic address:
In oxaliplatin-resistant gastric cancer (GC), multi-omics profiling combined with organoid libraries reveals altered metabolic pathways associated with chemoresistance. We identify a novel lactylation modification at K115 of Poly(RC)-binding protein 2 (PCBP2K115la), which confers functional oxaliplatin resistance. Mechanistic studies demonstrate that the long non-coding RNA BASP1-AS1 assembles a complex containing Unc-51 Like Autophagy Activating Kinase 1 (ULK1) and lactate dehydrogenase A (LDHA), thereby activating LDHA enzymatic activity to increase lactate production.
View Article and Find Full Text PDFOncol Rep
November 2025
Department of Lung Oncology, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin 130021, P.R. China.
Lung cancer is a common malignancy that poses risks to human health and quality of life. The primary treatment options currently available include surgery, chemotherapy and radiotherapy. However, the aggressive metastatic nature of the disease combined with the development of drug and radiation resistance results in suboptimal survival outcomes.
View Article and Find Full Text PDFHistol Histopathol
September 2025
Department of Cardiology, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
Lactate, as an end-product of glycolysis, has been considered as a metabolic waste that participates in a few physiological functions. Recently, a novel study by Zhao's laboratory reported that lactate can serve as an epigenetic modification substrate, causing histone or nonhistone lysine residues to undergo lactylation, which then regulates gene transcription, translation, and protein function. Subsequent studies confirmed that lactylation plays an important role in a series of physiological and pathological processes, such as inflammation, cancer, and other biological processes.
View Article and Find Full Text PDFInt J Biol Macromol
September 2025
Department of Neurosurgery, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou 412000, Hunan, China. Electronic address:
Glioblastoma (GBM) stands as one of the most formidable and deadly brain cancers, with temozolomide (TMZ) established as the primary chemotherapeutic agent. However, over 50 % of patients showed innate or acquired resistance. Sirtuins, a family of NAD-dependent deacetylases, have gained recognition as key regulators in shaping epigenetic landscapes and influencing chemoresistance across various cancers, yet their specific contribution to TMZ resistance in GBM has remained largely unexplored.
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