Retinol binding protein 1‐dependent activation of NF‐ κB signaling enhances the malignancy of non‐glioblastomatous diffuse gliomas
Wei Wu, Yichang Wang, Chen Niu, Alafate Wahafu, Longwei Huo, Xiaoye Guo, Jianyang Xiang, Xiaodong Li, Wanfu Xie, Xiaobin Bai, Maode Wang, Jia Wang
Abstract
Abstract 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 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 upregulated in the IDH WT 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 α (TNFα)–NF‐κB signaling. Moreover, exogenous silencing of RBP1 reduced phosphorylation of IkB‐kinase α (IKKα) and thus decreased NF‐κB expression via decreasing the degradation of the IκBα protein. Altogether, these data suggested RBP1‐dependent activation of NF‐κB signaling promoted malignancy of non‐GDG, indicating that RBP1 could be a reliable prognostic biomarker and potential therapeutic target for non‐GDG.