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Updated: Jun 20, 2025
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Global Level Quantification of Histone Post-Translational Modifications in a 3D Cell Culture Model of Hepatic Tissue
Published on: May 5, 2022
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Histone lactylation facilitates hepatocellular carcinoma progression by upregulating endothelial cell-specific
Peng Zhao1, Chunzhong Qiao1, Jiawei Wang1
1Department of General Surgery, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, Jiangsu, China.
Molecular Carcinogenesis
|July 17, 2024
Summary
Histone lactylation promotes hepatocellular carcinoma (HCC) growth and metastasis by increasing ESM1 expression. Inhibiting histone lactylation with 2-DG offers a potential therapeutic strategy for HCC.
Area of Science:
- Epigenetics and Cancer Biology
- Molecular Oncology
Background:
- Hepatocellular carcinoma (HCC) is a prevalent malignancy with complex epigenetic regulation.
- Histone lactylation is an emerging epigenetic modification implicated in various cancers, but its role in HCC remains unexplored.
Purpose of the Study:
- To investigate the functional role and molecular mechanisms of histone lactylation in HCC progression.
- To identify specific histone lactylation sites and their association with HCC prognosis.
- To explore the downstream targets and therapeutic potential of targeting histone lactylation in HCC.
Main Methods:
- Assessed histone lactylation levels in HCC tissues and cells using densitometry and western blot.
- Conducted in vitro functional assays and in vivo xenograft models to evaluate the impact of histone lactylation on HCC phenotypes.
- Utilized ChIP assays to investigate the interaction between histone lactylation and ESM1.
- Performed gain-and-loss-of-function assays for ESM1 and therapeutic intervention with 2-deoxy-d-glucose (2-DG).
Main Results:
- Histone lactylation levels, specifically H3K9 lactylation (H3K9la) and H3K56 lactylation (H3K56la), were elevated in HCC and correlated with poor prognosis.
- Histone lactylation promoted HCC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro.
- Inhibition of histone lactylation by 2-DG reduced malignant phenotypes, tumor growth, and metastasis in vivo.
- Histone lactylation was found to activate ESM1 transcription, which plays a carcinogenic role in HCC.
Conclusions:
- Histone lactylation enhances HCC cell malignancy, tumor growth, and metastasis by upregulating ESM1 expression.
- Targeting histone lactylation, potentially via 2-DG, represents a novel therapeutic strategy for HCC.
- This study elucidates a key downstream molecular mechanism of histone lactylation in HCC pathogenesis.
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