C18 ceramide plays an important role in the occurrence and development of oral squamous cell carcinoma. However, the function of ceramide synthase 1, a key enzyme in C18 ceramide synthesis, in oral squamous cell carcinoma is still unclear. The aim of our study was to investigate the relationship between ceramide synthase 1 and oral cancer. In this study, we found that the expression of ceramide synthase 1 was downregulated in oral cancer tissues and cell lines. In a mouse oral squamous cell carcinoma model induced by 4-nitroquinolin-1-oxide, ceramide synthase 1 knockout was associated with the severity of oral malignant transformation. Immunohistochemical studies showed significant upregulation of PCNA, MMP2, MMP9, and BCL2 expression and downregulation of BAX expression in the pathological hyperplastic area. In addition, ceramide synthase 1 knockdown promoted cell proliferation, migration, and invasion in vitro. Overexpression of CERS1 obtained the opposite effect. Ceramide synthase 1 knockdown caused endoplasmic reticulum stress and induced the VEGFA upregulation. Activating transcription factor 4 is responsible for ceramide synthase 1 knockdown caused VEGFA transcriptional upregulation. In addition, mild endoplasmic reticulum stress caused by ceramide synthase 1 knockdown could induce cisplatin resistance. Taken together, our study suggests that ceramide synthase 1 is downregulated in oral cancer and promotes the aggressiveness of oral squamous cell carcinoma and chemotherapeutic drug resistance.

C18神经酰胺在口腔鳞状细胞癌的发生发展中起重要作用。然而，神经酰胺合酶1（C18神经酰胺合成的关键酶）在口腔鳞状细胞癌中的作用仍不清楚。我们研究的目的是调查神经酰胺合酶 1 与口腔癌之间的关系。在本研究中，我们发现神经酰胺合酶 1 在口腔癌组织和细胞系中的表达下调。在 4-nitroquinolin-1-oxide 诱导的小鼠口腔鳞状细胞癌模型中，神经酰胺合酶 1 敲除与口腔恶性转化的严重程度相关。免疫组化研究显示病理增生区 PCNA、MMP2、MMP9 和 BCL2 表达显着上调，BAX 表达下调。此外，神经酰胺合酶 1 的敲低在体外促进细胞增殖、迁移和侵袭。CERS1的过表达获得了相反的效果。神经酰胺合酶 1 敲低引起内质网应激并诱导 VEGFA 上调。激活转录因子 4 是神经酰胺合酶 1 敲低导致 VEGFA 转录上调的原因。此外，神经酰胺合酶1敲低引起的轻度内质网应激可诱导顺铂耐药。总之，我们的研究表明神经酰胺合酶 1 在口腔癌中下调，并促进口腔鳞状细胞癌的侵袭性和化疗药物耐药性。神经酰胺合酶 1 敲低引起内质网应激并诱导 VEGFA 上调。激活转录因子 4 是神经酰胺合酶 1 敲低导致 VEGFA 转录上调的原因。此外，神经酰胺合酶1敲低引起的轻度内质网应激可诱导顺铂耐药。总之，我们的研究表明神经酰胺合酶 1 在口腔癌中下调，并促进口腔鳞状细胞癌的侵袭性和化疗药物耐药性。神经酰胺合酶 1 敲低引起内质网应激并诱导 VEGFA 上调。激活转录因子 4 是神经酰胺合酶 1 敲低导致 VEGFA 转录上调的原因。此外，神经酰胺合酶1敲低引起的轻度内质网应激可诱导顺铂耐药。总之，我们的研究表明神经酰胺合酶 1 在口腔癌中下调，并促进口腔鳞状细胞癌的侵袭性和化疗药物耐药性。