SP1 transcriptionally activates NLRP6 inflammasome and induces immune evasion and radioresistance in glioma cells

Glioma accounts for approximately 80% of all malignant brain tumors. This study aimed to investigate the interaction between specificity protein 1 (SP1) and NLR family pyrin domain containing 6 (NLRP6) and their roles in the activity of glioma cells. Differentially expressed genes in glioma were identified using transcriptome analysis tools, and a protein-protein-interaction network was performed based on the DEGs. SP1 and NLRP6 were abundantly expressed in glioma cells and indicated unfavorable prognosis of patients according to the GEO datasets. SP1could bind to the promoter of NLRP6 and induce its transcriptional activity. Downregulation of SP1 reduced proliferation, migration and invasion of glioma U87 cells in vitro as well as tumorigenesis in vivo. The malignancy of cells was restored after NLRP6 upregulation. Downregulation of SP1 in glioma cells also increased proliferation of CD8+ T cells and the immune activity in U87 cells, and it reduced the radioresistance of U87 cells. However, the immune evasion and radioresistance of glioma cells were restored upon NLRP6 upregulation. NLRP6 mediated the innate immune pathway through an ASC/caspase-1/IL-1β axis. To conclude, this study suggested that SP1 interacts with NLRP6 inflammasome to enhance malignant behaviors, immune evasion and radioresistance in glioma cells.