Introduction Head and neck squamous cell carcinoma (HNSCC) is characterized by metabolic reprogramming and poor prognosis. While lactate accumulates in HNSCC, how upstream RNA regulation coordinates lactate-associated epigenetic alterations during tumor progression remains unclear. Methods We integrated TCGA-HNSCC analyses, paired clinical specimens, and in vitro functional assays with mechanistic readouts including RIP-qPCR and LDHA 3′UTR luciferase reporters. Lactate was quantified in culture supernatants, H4K8la was assessed by immunoblotting and tissue IF, and H4K8la CUT exogenous lactate partially restored H4K8la under pH-matched conditions. Exploratory H4K8la CUT&Tag suggested increased H4K8la signal at the E2F2 locus with enrichment of cell-cycle programs upon lactate treatment. Conclusion These findings support an IGF2BP3-LDHA-lactate-H4K8la axis linking post-transcriptional regulation to metabolic and chromatin remodeling in HNSCC.
Wu et al. (Wed,) studied this question.