GNB4 Silencing Promotes Pyroptosis to Inhibit the Development of Glioma by Activating cGAS-STING Pathway

The induction of immunogenic cell death is a promising therapeutic option for gliomas. Pyroptosis is a type of programmed immunogenic cell death and its role in gliomas remains unclear. Differentially expressed genes (DEGs) were obtained from GSE4290 and GSE31262 datasets. Hub genes were screened from protein-protein interaction networks and assessed using principal component analysis and receiver operating characteristic curves. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the mRNA expression of hub genes. Pyroptosis and pathway-related proteins were assessed using western blotting. Inflammatory factor levels were determined using enzyme-linked immunosorbent assay. The effect of guanine nucleotide-binding protein-4 (GNB4) on proliferation, migration, and invasion was evaluated using a cell viability test kit and wound-healing and transwell assays. In total, 202 DEGs were identified. Among them, F2R, GNG4, GNG3, PRKCB, and GNB4 were identified as hub genes in gliomas after comprehensive bioinformatics analysis. GNB4 was significantly upregulated in glioma cells compared to normal brain glial cells. Silencing GNB4 significantly inhibited proliferation, invasion, and migration of glioma cells. The expression of pyroptosis-related proteins increased after GNB4 silencing, with elevated levels of inflammatory factors. Pyroptosis inhibitors reversed the inhibitory effects of GNB4 silencing on cell proliferation, migration, and invasion. Additionally, GNB4 silencing activated the cGAS-STING pathway. Treatment with a cGAS-STING pathway inhibitor reversed the inhibition of proliferation, migration, and invasion while downregulating the expression of pyroptosis-related proteins. Silencing GNB4 promotes Pyroptosis and thus inhibits the proliferation, migration, and invasion of glioma cells by activating the cGAS-STING pathway, which is a promising biomarker and therapeutic target for glioma.

GNB4; Glioma; Hub genes; Pyroptosis.