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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 wel...

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Autores principales: Wu, Wei, Wang, Yichang, Niu, Chen, Wahafu, Alafate, Huo, Longwei, Guo, Xiaoye, Xiang, Jianyang, Li, Xiaodong, Xie, Wanfu, Bai, Xiaobin, Wang, Maode, Wang, Jia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8819305/
https://www.ncbi.nlm.nih.gov/pubmed/34866280
http://dx.doi.org/10.1111/cas.15233
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author Wu, Wei
Wang, Yichang
Niu, Chen
Wahafu, Alafate
Huo, Longwei
Guo, Xiaoye
Xiang, Jianyang
Li, Xiaodong
Xie, Wanfu
Bai, Xiaobin
Wang, Maode
Wang, Jia
author_facet Wu, Wei
Wang, Yichang
Niu, Chen
Wahafu, Alafate
Huo, Longwei
Guo, Xiaoye
Xiang, Jianyang
Li, Xiaodong
Xie, Wanfu
Bai, Xiaobin
Wang, Maode
Wang, Jia
author_sort Wu, Wei
collection PubMed
description 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.
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spelling pubmed-88193052022-02-11 Retinol binding protein 1‐dependent activation of NF‐ κB signaling enhances the malignancy of non‐glioblastomatous diffuse gliomas Wu, Wei Wang, Yichang Niu, Chen Wahafu, Alafate Huo, Longwei Guo, Xiaoye Xiang, Jianyang Li, Xiaodong Xie, Wanfu Bai, Xiaobin Wang, Maode Wang, Jia Cancer Sci Original Articles 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. John Wiley and Sons Inc. 2021-12-15 2022-02 /pmc/articles/PMC8819305/ /pubmed/34866280 http://dx.doi.org/10.1111/cas.15233 Text en © 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Wu, Wei
Wang, Yichang
Niu, Chen
Wahafu, Alafate
Huo, Longwei
Guo, Xiaoye
Xiang, Jianyang
Li, Xiaodong
Xie, Wanfu
Bai, Xiaobin
Wang, Maode
Wang, Jia
Retinol binding protein 1‐dependent activation of NF‐ κB signaling enhances the malignancy of non‐glioblastomatous diffuse gliomas
title Retinol binding protein 1‐dependent activation of NF‐ κB signaling enhances the malignancy of non‐glioblastomatous diffuse gliomas
title_full Retinol binding protein 1‐dependent activation of NF‐ κB signaling enhances the malignancy of non‐glioblastomatous diffuse gliomas
title_fullStr Retinol binding protein 1‐dependent activation of NF‐ κB signaling enhances the malignancy of non‐glioblastomatous diffuse gliomas
title_full_unstemmed Retinol binding protein 1‐dependent activation of NF‐ κB signaling enhances the malignancy of non‐glioblastomatous diffuse gliomas
title_short Retinol binding protein 1‐dependent activation of NF‐ κB signaling enhances the malignancy of non‐glioblastomatous diffuse gliomas
title_sort retinol binding protein 1‐dependent activation of nf‐ κb signaling enhances the malignancy of non‐glioblastomatous diffuse gliomas
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8819305/
https://www.ncbi.nlm.nih.gov/pubmed/34866280
http://dx.doi.org/10.1111/cas.15233
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