Global Lactylation Profiling Reveals Lactate-Driven Regulatory Mechanisms Promoting Tumor Progression in Oral Squamous Cell Carcinoma [RNA-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. 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.

肿瘤细胞通常依赖有氧糖酵解进行代谢，而乳酰化（lactylation）作为一种新近发现的翻译后修饰，可显著影响分子生物学过程。本研究全面解析了乳酰化在口腔鳞状细胞癌（oral squamous cell carcinoma, OSCC）中的作用，为理解其对肿瘤进展的影响提供了初步见解。本研究对乳酸处理前后的口腔鳞状细胞癌细胞系开展了CUT&TAG、ATAC及转录组测序，并通过染色质免疫沉淀定量PCR（ChIP-qPCR）与实时定量逆转录PCR（RT-qPCR）实验验证了口腔鳞状细胞癌组织中的检测结果。整合分析共鉴定出217个在口腔鳞状细胞癌中受乳酰化驱动且表达上调的基因。乳酰化可广泛影响肿瘤相关通路，尤其对PI3K/AKT与MAPK信号通路具有显著调控作用。本项开创性研究从染色质驱动的基因表达视角出发，系统绘制了乳酰化在口腔鳞状细胞癌中的全局调控图谱。本研究将CAL27细胞以10mM乳酸处理24小时后，针对乳酰化修饰开展CUT&TAG-seq测序、ATAC-seq测序，并同步进行下游RNA-seq测序。