Histone lactylation-driven feedback loop modulates pyrimidine metabolism to promote oral carcinogenesis - PubMed
3 hours ago
- #metabolic reprogramming
- #histone lactylation
- #oral carcinogenesis
- Histone lactylation, particularly H3K18la, is elevated in oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC) tissues.
- Inhibition of histone lactylation represses malignant phenotypes in OLK and OSCC cells, both in vitro and in vivo.
- Glycolysis inhibitors block precancerous lesions and OSCC formation in a 4NQO-induced tongue carcinogenesis model.
- H3K18la activates thymidine kinase 1 (TK1) transcription, increasing pyrimidine biosynthesis and promoting oral carcinogenesis.
- TK1 downregulation inhibits the Wnt signaling pathway via RhoA, and Wnt/β-catenin inhibitor XAV939 reduces lactate and H3K18la levels.
- A glycolysis/H3K18la/TK1/β-catenin positive feedback loop exacerbates dysfunction in OSCC initiation.
- The study reveals a novel link between epigenetic regulation and lactate-driven metabolic reprogramming in OSCC.