Global Lactylation Profiling Reveals Lactate-Driven Regulatory Mechanisms Promoting Tumor Progression in Oral Squamous Cell Carcinoma [ATAC-seq]

Cancer cells often rely on aerobic glycolysis for metabolism, and lactylation, a newly discovered post-translational modification, significantly impacts molecular processes. This study comprehensively analyzes lactylation's role in oral squamous cell carcinoma (OSCC), providing initial insights into its impact on progression. Oral squamous cell carcinoma cell lines, before and after lactate treatment, underwent CUT&TAG, ATAC, and transcriptomic sequencing. ChIP-qPCR and RT-qPCR validated results in OSCC tissues. Integrated analysis identified 217 genes with increased expression driven by lactylation in OSCC. Lactylation broadly impacted pathways in cancer, notably regulating PI3K/AKT and MAPK signaling. This pioneering study analyzes lactylation in OSCC, providing a global map of its regulation in oral squamous cell carcinoma from the perspective of chromatin-driven gene expression. Overall design: Treating CAL27 cells with 10mM lactate for 24 hours, we conducted CUT&TAG-seq on lactylation modification and ATAC-seq, along with downstream RNA-seq.