gp96 knockdown inhibits the malignant behaviors of glioblastoma cells by suppressing the NF-κB pathway

Abstract

Glioblastoma (GBM) is the most aggressive primary brain tumor and has a dismal prognosis. The chaperone protein gp96 is implicated in various cancers but its role and functions in GBM remain poorly defined. This study aimed to investigate the expression, function, and underlying mechanism of gp96 in GBM pathogenesis. gp96 expression was analyzed via the GEPIA2 database. The cell counting kit-8, EdU staining, colony formation and transwell assays were performed to evaluate viability, proliferation, invasion and migration of GBM cell lines. The underlying mechanism was investigated by Kyoto Encyclopedia of Genes and Genomes analysis and Western blot. The results showed that gp96 mRNA and protein levels were upregulated in GBM cells and that gp96 knockdown significantly inhibited viability, proliferation, migration and invasion by the cells. gp96 was found to be enriched in the NF-κB pathway and gp96 knockdown inhibited NF-κB pathway activation in the GBM cells. The NF-κB activator phorbol 12-myristate 13-acetate restored the viability, proliferation, migration, and invasion inhibited by gp96 knockdown. Thus, our findings revealed that gp96 knockdown inhibited the malignant behaviors of GBM by suppressing the NF-κB pathway. This study identifies the gp96/NF-κB axis as a novel potential therapeutic target for GBM intervention.