Lactylation, a post-translational modification, is increasingly recognized for its role in cancer progression. This study investigates its prevalence and impact in oral squamous cell carcinoma (OSCC). Immunohistochemical staining of 81 OSCC cases shows lactylation levels correlate with malignancy grading. Proteomic analyses of six OSCC tissue pairs reveal 2765 lactylation sites on 1033 proteins, highlighting its extensive presence. These modifications influence metabolic processes, molecular synthesis, and transport. CAL27 cells are subjected to cleavage under targets and tagmentation assay for accessible-chromatin with high-throughput sequencing, and transcriptomic sequencing pre- and post-lactate treatment, with 217 genes upregulated due to lactylation. Chromatin immunoprecipitation-quantitative PCR and real-time fluorescence quantitative PCR confirm the regulatory role of lactylation at the K146 site of dexh-box helicase 9 (DHX9), a key factor in OSCC progression. CCK8, colony formation, scratch healing, and Transwell assays demonstrate that lactylation mitigates the inhibitory effect of DHX9 on OSCC, thereby promoting its occurrence and development. Lactylation actively modulates gene expression in OSCC, with significant effects on chromatin structure and cellular processes. This study provides a foundation for developing targeted therapies against OSCC, leveraging the role of lactylation in disease pathogenesis.

中文翻译：

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多组学揭示了乳酸化驱动的调节机制促进口腔鳞状细胞癌的肿瘤进展


乳酰化是一种翻译后修饰，因其在癌症进展中的作用而日益得到认可。本研究调查了其在口腔鳞状细胞癌 （OSCC） 中的患病率和影响。81 例 OSCC 病例的免疫组织化学染色显示乳酸化水平与恶性肿瘤分级相关。对 6 对 OSCC 组织进行的蛋白质组学分析揭示了 1033 种蛋白质上的 2765 个乳酰化位点，突出了其广泛的存在。这些修饰会影响代谢过程、分子合成和运输。CAL27 细胞在靶标下进行切割，并通过高通量测序对可接近的染色质进行标记测定，并在乳酸前后处理进行转录组测序，其中 217 个基因由于乳酰化而上调。染色质免疫沉淀定量 PCR 和实时荧光定量 PCR 证实了 dexh 盒解旋酶 9 （DHX9） K146 位点乳酰化的调节作用，这是 OSCC 进展的关键因素。CCK8、集落形成、划痕愈合和 Transwell 检测表明，乳酰化减轻了 DHX9 对 OSCC 的抑制作用，从而促进其发生和发展。乳酰化积极调节 OSCC 中的基因表达，对染色质结构和细胞过程有显著影响。本研究为开发针对 OSCC 的靶向疗法提供了基础，利用乳酸化在疾病发病机制中的作用。