RBP1-dependent activation of NF- κB signaling enhances malignancy of the non-glioblastomatous diffuse gliomas.

The non-glioblastomatous diffuse gliomas (non-GDG) is a heterogeneous neuroepithelial tumor and exhibits a varied survival range from 4 to 13 years based on the diverse subtypes. Recent studies demonstrated novel molecular markers can predict prognosis for the non-GDG patients, however, these findings as well as pathological classification strategies show obvious limitations on malignant transition due to the heterogeneity among the non-GDGs. Therefore, developing reliable prognostic biomarkers and therapeutic targets become an urgent need for precisely distinguishing the non-GDG subtypes, illuminating the underlying mechanism. Nuclear factor-κβ (NF-κB) has been proved to be a significant nuclear transcriptional regulator with specific DNA-binding sequences to participate in multiple pathophysiological processes. However, the underlying mechanism of NF-κB activation still needs to be further investigated. Herein, our results indicated retinol binding protein 1 (RBP1) was significantly up-regulated in the IDHWT and 1p19qNon co-del non-GDG subtypes and enriched RBP1 expression was markedly correlated with more severe outcomes. Additionally, malignant signatures of the non-GDG cells including proliferation, migration, invasion and self-renewal were significantly suppressed by lentiviral knock-down of RBP1. To further explore the underlying molecular mechanism, bioinformatics analysis was performed using databases and the results demonstrated RBP1 was strongly correlated to tumor necrosis factor α (TNFα)-NF-κB signaling. Moreover, exogenous silencing of RBP1 reduced phosphorylation of IkB-kinase α (IKKα) thus decreased NF-κB expression via decreasing degradation of IκBα protein. Altogether, these data suggested RBP1-dependent activation of NF-κB signaling promoted malignancy of the non-GDG, indicating that RBP1 could be a reliable prognostic biomarker and potential therapeutic target for the non-GDG.