DDB2通过激活NF-κB通路促进胶质瘤上皮-间充质转化

Abstract

Glioblastoma (GBM), the most prevalent primary brain tumor, is characterized by rapid proliferation, invasive growth patterns, and poor clinical outcomes. This study investigates the expression and clinical significance of DNA damage-binding protein 2(DDB2) in GBM, aiming to identify potential prognostic biomarkers and therapeutic targets. In this study, we demonstrated that DDB2 expression was negatively associated with patient prognosis in GBM patients. DDB2 knockdown inhibited the proliferation, invasion, and migration capacity of U87 and LN229 cells. In vivo, DDB2 knockdown inhibited the growth of xenograft tumors derived from inoculated GBM cells. DDB2 knockdown inhibited epithelial-mesenchymal transition (EMT) in U87 and LN229 cells. Mechanistically, DDB2 down-regulation led to the inhibition of nuclear translocation of P65 subunit, which inhibited the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway and resulted in the reduced expression of EMT-related transcription factors. Taken together, the present study demonstrates that DDB2 promotes EMT by activating the NF-κB pathway in GBM. These findings provide new insights into the role of DDB2 in GBM, suggesting that DDB2 could serve as a potential therapeutic target and prognostic marker for this malignancy.