Histone lactylation promotes malignant progression by facilitating USP39 expression to target PI3K/AKT/HIF-1α signal pathway in endometrial carcinoma
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View abstract on PubMed
Summary
This summary is machine-generated.Histone lactylation, a key epigenetic modification, promotes endometrial cancer (EC) progression by increasing cell proliferation and migration. Inhibiting lactylation offers a potential therapeutic strategy for EC.
Area Of Science
- Oncology
- Epigenetics
- Biochemistry
Background
- Histone lactylation is implicated in tumorigenesis but its role in endometrial carcinoma (EC) remains unclear.
- Understanding the regulatory mechanisms of histone lactylation in EC is crucial for developing targeted therapies.
Purpose Of The Study
- To investigate the role and regulatory mechanism of histone lactylation in endometrial carcinoma progression.
- To evaluate the therapeutic potential of targeting histone lactylation in EC.
Main Methods
- Immunohistochemistry and western blot were used to assess global lactylation levels in EC tissues.
- Experiments involving 2-deoxy-d-glucose (2-DG) and oxamate were conducted to modulate lactylation and assess its effects on EC cells.
- Molecular mechanisms involving USP39, PI3K/AKT/HIF-1α pathway, and PGK1 were investigated.
Main Results
- Global lactylation levels were found to be elevated in EC tissues.
- Inhibition of lactylation using 2-DG and oxamate reduced EC cell proliferation and migration, induced apoptosis, and arrested the cell cycle.
- Histone lactylation was shown to stimulate USP39 expression, which in turn activated the PI3K/AKT/HIF-1α pathway by stabilizing PGK1, thereby promoting glycolysis and tumor progression.
Conclusions
- Histone lactylation is a significant driver of endometrial carcinoma progression.
- Targeting histone lactylation and its downstream pathways presents a promising therapeutic avenue for endometrial cancer treatment.
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