Retinol binding protein 1-dependent activation of NF- κB signaling enhances the malignancy of non-glioblastomatous diffuse gliomas

Nonglioblastomatous diffuse glioma (non-GDG) is a heterogeneous neuroepithelial tumor that 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 non-GDG patients; however, these findings as well as pathological classification strategies show obvious limitations on malignant transition due to the heterogeneity among non-GDGs. Therefore, developing reliable prognostic biomarkers and therapeutic targets have become an urgent need for precisely distinguishing non-GDG subtypes, illuminating the underlying mechanism. Nuclear factor kappa beta (NF-kappa B) 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-kappa B activation still needs to be further investigated. Herein, our results indicated retinol-binding protein 1 (RBP1) was significantly upregulated in the IDHWT and 1p19q(Non 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 knockdown of RBP1. To further explore the underlying molecular mechanism, bioinformatics analysis was performed using databases, and the results demonstrated RBP1 was strongly correlated with tumor necrosis factor alpha (TNF alpha)-NF-kappa B signaling. Moreover, exogenous silencing of RBP1 reduced phosphorylation of IkB-kinase alpha (IKK alpha) and thus decreased NF-kappa B expression via decreasing the degradation of the I kappa B alpha protein. Altogether, these data suggested RBP1-dependent activation of NF-kappa B signaling promoted malignancy of non-GDG, indicating that RBP1 could be a reliable prognostic biomarker and potential therapeutic target for non-GDG.

Automated summary

Studies have shown that RBP1 is a significant potential therapeutic target that relies on the NF-kappa B signaling pathway, and its expression is closely associated with the malignancy of non-GDG neuroepithelial tumors.