Abstract
BACKGROUND: Renal cell carcinoma (RCC), a frequently diagnosed tumor type, serves as the focus of our investigation into the functional role of the alanine serine cysteine transporter 2 (ASCT2) gene and its potential molecular mechanisms. This study elucidates ASCT2's function in the pathogenesis of RCC and its underlying molecular mechanisms. METHODS: Individuals diagnosed with RCC were collected from Gaoxin Branch of the First Affiliated Hospital of Nanchang University. Quantitative polymerase chain reaction (qPCR), fluorescence immunostaining, proteomic blotting analysis, and gene overexpression were employed to elucidate the contribution of ASCT2 in sustaining the malignant phenotype of RCC and to dissect its influence on the pyroptosis. RESULTS: ASCT2 RCC specimens exhibited reduced messenger ribonucleic acid (mRNA) and protein expression levels. Overall survival rates and recurrence-free intervals with high expression of ASCT2 in individuals diagnosed with RCC were higher than those of ASCT2 low expression. ASCT2 gene overexpression inhibited cellular proliferation kinetics and migratory capacity, while suppressing 5-ethynyl-2'-deoxyuridine (EdU) incorporation in vitro. ASCT2 gene inhibition increased cellular proliferation and motility rate, and promoted EdU-labelled cells within the cultured system. NOD-like receptor thermal protein domain associated protein 3 (NLRP3) agonist simultaneously counteracted the influences of ASCT2 siRNA (si-ASCT2) on NLRP3-GSDMD protein complex expressions and cellular proliferation in an in vitro system. NLRP3 inhibitor reversed the impact of ASCT2 on NLRP3/GSDMD protein expressions and in an in vitro cellular proliferation assay. NLRP3 inhibitor increased ASCT2-mediated impacts on migration rate and EdU-positive cells in cultured cell system. NLRP3 agonist reduced the effects of si-ASCT2 on cellular migratory capacity and EdU incorporation in the cultured system. CONCLUSIONS: This research focuses on ASCT2's role in RCC, and specifically examines ASCT2-mediated modulation of the NLRP3 inflammasome and pyroptosis. ASCT2 knockdown in RCC cells inhibited proliferation and migration, while overexpression of ASCT2 thereby enhanced pyroptosis, providing a new model for RCC pathogenesis and treatment.