Downregulation of ceramide synthase 1 promotes oral cancer through endoplasmic reticulum stress / 国际口腔科学杂志·英文版

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.

Differential proteomics research on exosomes derived from tongue squamous cell carcinoma cells and normal mucosa cells / 华西口腔医学杂志

<p><b>OBJECTIVE</b>This study aimed to explore further the mechanisms of tongue squamous cell carcinoma (TSCC) cell recurrence, metastasis, and diffusion, as well as to establish the experimental basis for the molecular biology research on TSSC. We intend to complete our objective through differential proteomics and preliminary analysis protein expression of exosomes derived from TSCC and normal mucosa cells.</p><p><b>METHODS</b>We acquired cultured supernatant fluid in vitro in the laboratory by culturing TSCC (tongue cancer Tca8113 cell line) and human normal mucosa cells (HOK cell line). The exosomes were separated and purified through differential centrifugation. Furthermore, the different protein expressions were identified through dielectrophoresis and mass spectrometry. The functions of the different protein expressions were identified through an online database search.</p><p><b>RESULTS</b>TSCC and human normal mucosa cells secrete a large amount of capsule bubble structure substances in vitro, as confirmed by electron microscopy and surface markers heat shock protein-70 and major histocompatibility complex class 1. A total of 16 oral cancer cell-derived exosomes that expressed quantity more than two times, twelve that increased their expression levels, and four that cut their expressions were identified through the differential proteomics research on the two groups.</p><p><b>CONCLUSION</b>Differential proteins that were verified through the online database serve an important function in exosome formation and in the progress of cancer.</p>