Periostin-mediated activation of NF-κB signaling promotes tumor progression and chemoresistance in glioblastoma.

Glioblastoma (GBM) is the most aggressive form of diffuse glioma, characterized by high lethality. Temozolomide (TMZ)-based chemotherapy is a standard treatment for GBM, but development of chemoresistance poses a significant therapeutic challenge. Despite advances in understanding GBM biology, the mechanisms driving TMZ resistance remain unclear. Identifying vital molecular players involved in this resistance is crucial for developing new therapies. Our results indicated that periostin (POSTN) was significantly upregulated in GBM cell lines and patient samples, correlating with poorer clinical outcomes. POSTN overexpression enhanced GBM cell proliferation, migration, invasion, and chemoresistance, while lentiviral suppression of POSTN significantly reduced these behaviors. In vivo, bioluminescence imaging further confirmed the enhanced tumor growth associated with POSTN overexpression. Bioinformatics analysis was performed to explore the underlying molecular mechanism. The results revealed a strong correlation between POSTN and epithelial-mesenchymal transition (EMT) process and the tumor necrosis factor α (TNFα)-NF-κB signaling pathway. Moreover, exogenous POSTN silencing reduced IκB-kinase α (IKKα) phosphorylation, thereby decreasing NF-κB expression by limiting IκBα degradation. Collectively, our study demonstrated that POSTN-induced activation of NF-κB signaling and EMT processes promoted the malignancy and chemoresistance of GBM, suggesting that POSTN may serve as a reliable prognostic biomarker and potential therapeutic target for GBM.