School of Medicine, Lishui University, No 01, Rd Xueyuan Avenue, Lishui, 323000, Zhejiang, China.
BMC Oral Health. 2024 Apr 5;24(1):418. doi: 10.1186/s12903-024-04174-0.
Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy. The oncometabolites have been studied in OSCC, but the mechanism of metabolic reprogramming remains unclear. To identify the potential metabolic markers to distinguish malignant oral squamous cell carcinoma (OSCC) tissue from adjacent healthy tissue and study the mechanism of metabolic reprogramming in OSCC. We compared the metabolites between cancerous and paracancerous tissues of OSCC patients by HNMR analysis. We established OSCC derived cell lines and analyzed their difference of RNA expression by RNA sequencing. We investigated the metabolism of γ-aminobutyrate in OSCC derived cells by real time PCR and western blotting. Our data revealed that much more γ-aminobutyrate was produced in cancerous tissues of OSCC patients. The investigation based on OSCC derived cells showed that the increase of γ-aminobutyrate was promoted by the synthesis of glutamate beyond the mitochondria. In OSCC cancerous tissue derived cells, the glutamate was catalyzed to glutamine by glutamine synthetase (GLUL), and then the generated glutamine was metabolized to glutamate by glutaminase (GLS). Finally, the glutamate produced by glutamate-glutamine-glutamate cycle was converted to γ-aminobutyrate by glutamate decarboxylase 2 (GAD2). Our study is not only benefit for understanding the pathological mechanisms of OSCC, but also has application prospects for the diagnosis of OSCC.
口腔鳞状细胞癌 (OSCC) 是最常见的头颈部恶性肿瘤。代谢物在 OSCC 中已有研究，但代谢重编程的机制仍不清楚。为了确定潜在的代谢标志物，以区分恶性口腔鳞状细胞癌 (OSCC) 组织与相邻的健康组织，并研究 OSCC 中的代谢重编程机制。我们通过 HNMR 分析比较了 OSCC 患者癌组织和癌旁组织之间的代谢物。我们建立了 OSCC 衍生的细胞系，并通过 RNA 测序分析了它们的 RNA 表达差异。我们通过实时 PCR 和 Western blot 研究了 γ-氨基丁酸在 OSCC 衍生细胞中的代谢。我们的数据显示，OSCC 患者癌组织中产生了更多的 γ-氨基丁酸。基于 OSCC 衍生细胞的研究表明，γ-氨基丁酸的增加是由线粒体外谷氨酸的合成促进的。在 OSCC 癌组织衍生细胞中，谷氨酸被谷氨酰胺合成酶 (GLUL) 催化为谷氨酰胺，然后由谷氨酰胺酶 (GLS) 将生成的谷氨酰胺代谢为谷氨酸。最后，谷氨酸-谷氨酰胺-谷氨酸循环产生的谷氨酸被谷氨酸脱羧酶 2 (GAD2) 转化为 γ-氨基丁酸。我们的研究不仅有助于理解 OSCC 的病理机制，而且对 OSCC 的诊断也具有应用前景。
