Chemerin Promotes Oral Squamous Cell Carcinoma Progression via NLRP3-Mediated Pyroptosis and the GSDMD-N Pathway

ABSTRACT: Introduction and aims: Oral squamous cell carcinoma (OSCC) is a common malignant tumour of the head and neck region. In recent years, the relationship between pyroptosis and tumours has received increasing attention. However, its regulatory mechanism and effects on tumour behaviour remain unclear. The purpose of this study was to explore the effect of chemerin expression on pyroptosis of OSCC tumour cells and its underlying molecular mechanism. Methods: In this study, chemerin expression and pyroptosis-related proteins in 145 OSCC tissues were detected using immunohistochemical methods. The effect of chemerin expression on the expression of pyroptosis related proteins (GSDMD,GSDMD-N and IL-1β) in OSCC cells was explored by Western blot analysis. The influence of chemerin-induced pyroptosis on the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) and lipid metabolism of OSCC cells was investigated through scratch test, transwell, flow cytometry experiments and CCK-8 assays. Nude mice experiments were also done to explore the effects of chemerin expression on tumour cell pyroptosis and tumour growth. Results: Our findings suggested that elevated expression of chemerin enhances pyroptosis in OSCC cells both in vivo and in vitro. Pyoptosis-related proteins were highly expressed in OSCC, and Gasdermin D (GSDMD) expression was associated with poor clinical prognosis and short survival time in OSCC patients. The combination of chemerin and GSDMD expression was correlated with a poorer clinical prognosis. In vitro experimental results showed that pyroptosis of OSCC cells promoted cell proliferation by regulating cell cycles via increasing the number of cells entering the S phase, as well as cell invasion and migration through EMT. The pyroptosis of OSCC cells also affected lipid metabolism, promoting tumour progression. Conclusion: Our findings indicate that chemerin mostly facilitated pyroptosis of OSCC cells via the NLRP3/GSDMD-N pathway, and pyroptosis promoted tumor progression through different pathways. Both overexpression of chemerin and elevated pyroptosis in OSCC cells appear to be poor prognostic jndicators in OSCC.