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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. In this review, we summarize advanced achievements on the effects of lactylation in various diseases and potential treatment targets, providing a reference and direction for future research.
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http://dx.doi.org/10.14670/HH-18-980 | DOI Listing |
Int Immunopharmacol
August 2025
Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China; Shanghai Engineering Research Center of Lung Transplantation, Shanghai, China. Electronic address:
Background: Protein lactylation has been implicated in stress-responsive cellular mechanisms, yet its role in lung transplantation-associated ischemia-reperfusion injury (IRI) remains undefined.
Methods: Transcriptomic profiles from GSE145989 were analyzed through differential expression analysis (limma) and weighted gene co-expression network analysis (WGCNA). Integrating the identified genes with lactylation-related signatures uncovered key lactylation-related genes (LRGs) as potential targets.
Free 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 PDFActa Biochim Biophys Sin (Shanghai)
September 2025
Preeclampsia (PE) involves complex metabolic-inflammatory interactions, yet the mechanistic links among glycolysis, protein lactylation, and pyroptosis in placental pathogenesis remain undefined. In this study, we explore their tripartite relationship with PE development by combining bioinformatics analysis of PE-associated transcriptomes with experimental validation using placental tissues from PE patients and healthy controls. To elucidate the underlying mechanism, we utilize models involving hypoxic endothelial cell cultures, pharmacological glycolysis inhibition via 2-deoxyglucose, and genetic modulation of hexokinase 2 (HK2) expressions through siRNA silencing and plasmid-based overexpression.
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 PDF