RBM8A Promotes Glioblastoma Growth and Invasion Through the Notch/STAT3 Pathway

BackgroundGlioblastoma (GBM) is a prevalent brain malignancy with an extremely poor prognosis, which is attributable to its invasive biological behavior. The RNA-binding motif protein 8A (RBM8A) has different effects on various human cancers. However, the role of RBM8A in GBM progression remains unc...

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Autores principales:	Yan Lin, Lei Wei, Beiquan Hu, Jinyan Zhang, Jiazhang Wei, Zhongrun Qian, Donghua Zou
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	RBM8A glioblastoma prognosis Notch stat3 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/2d2e58881778431fab63031040069905
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spelling	oai:doaj.org-article:2d2e58881778431fab630310400699052021-11-04T07:54:41ZRBM8A Promotes Glioblastoma Growth and Invasion Through the Notch/STAT3 Pathway2234-943X10.3389/fonc.2021.736941https://doaj.org/article/2d2e58881778431fab630310400699052021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.736941/fullhttps://doaj.org/toc/2234-943XBackgroundGlioblastoma (GBM) is a prevalent brain malignancy with an extremely poor prognosis, which is attributable to its invasive biological behavior. The RNA-binding motif protein 8A (RBM8A) has different effects on various human cancers. However, the role of RBM8A in GBM progression remains unclear.MethodsWe investigated the expression levels of RBM8A in 94 GBM patients and explored the correlation between RBM8A expression and patient prognosis. Using in vitro and in vivo assays, combined with GBM sequencing data from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), we examined whether and how RBM8A contributes to GBM progression.ResultsRBM8A was up-regulated in GBM tissues, and its higher expression correlated with worse prognosis. Knockdown of RBM8A inhibited GBM progression and invasion ability both in vitro and in vivo. On the contrary, overexpression of RBM8A promoted GBM progression and invasion ability. Enrichment analysis of differentially expressed genes in GBM data identified the Notch1/STAT3 network as a potential downstream target of RBM8A, and this was supported by molecular docking studies. Furthermore, we demonstrated that RBM8A regulates the transcriptional activity of CBF1. The γ-secretase inhibitor DAPT significantly reversed RBM8A-enhanced GBM cell proliferation and invasion, and was associated with down-regulation of p-STAT3 and Notch1 protein. Finally, the gene set variance analysis score of genes involved in regulation of the Notch1/STAT3 network by RBM8A showed good diagnostic and prognostic value for GBM.ConclusionsRBM8A may promote GBM cell proliferation and migration by activating the Notch/STAT3 pathway in GBM cells, suggesting that RBM8A may serve as a potential therapeutic target for the treatment of GBM.Yan LinLei WeiBeiquan HuJinyan ZhangJiazhang WeiZhongrun QianDonghua ZouFrontiers Media S.A.articleRBM8AglioblastomaprognosisNotchstat3Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	RBM8A glioblastoma prognosis Notch stat3 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	RBM8A glioblastoma prognosis Notch stat3 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Yan Lin Lei Wei Beiquan Hu Jinyan Zhang Jiazhang Wei Zhongrun Qian Donghua Zou RBM8A Promotes Glioblastoma Growth and Invasion Through the Notch/STAT3 Pathway
description	BackgroundGlioblastoma (GBM) is a prevalent brain malignancy with an extremely poor prognosis, which is attributable to its invasive biological behavior. The RNA-binding motif protein 8A (RBM8A) has different effects on various human cancers. However, the role of RBM8A in GBM progression remains unclear.MethodsWe investigated the expression levels of RBM8A in 94 GBM patients and explored the correlation between RBM8A expression and patient prognosis. Using in vitro and in vivo assays, combined with GBM sequencing data from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), we examined whether and how RBM8A contributes to GBM progression.ResultsRBM8A was up-regulated in GBM tissues, and its higher expression correlated with worse prognosis. Knockdown of RBM8A inhibited GBM progression and invasion ability both in vitro and in vivo. On the contrary, overexpression of RBM8A promoted GBM progression and invasion ability. Enrichment analysis of differentially expressed genes in GBM data identified the Notch1/STAT3 network as a potential downstream target of RBM8A, and this was supported by molecular docking studies. Furthermore, we demonstrated that RBM8A regulates the transcriptional activity of CBF1. The γ-secretase inhibitor DAPT significantly reversed RBM8A-enhanced GBM cell proliferation and invasion, and was associated with down-regulation of p-STAT3 and Notch1 protein. Finally, the gene set variance analysis score of genes involved in regulation of the Notch1/STAT3 network by RBM8A showed good diagnostic and prognostic value for GBM.ConclusionsRBM8A may promote GBM cell proliferation and migration by activating the Notch/STAT3 pathway in GBM cells, suggesting that RBM8A may serve as a potential therapeutic target for the treatment of GBM.
format	article
author	Yan Lin Lei Wei Beiquan Hu Jinyan Zhang Jiazhang Wei Zhongrun Qian Donghua Zou
author_facet	Yan Lin Lei Wei Beiquan Hu Jinyan Zhang Jiazhang Wei Zhongrun Qian Donghua Zou
author_sort	Yan Lin
title	RBM8A Promotes Glioblastoma Growth and Invasion Through the Notch/STAT3 Pathway
title_short	RBM8A Promotes Glioblastoma Growth and Invasion Through the Notch/STAT3 Pathway
title_full	RBM8A Promotes Glioblastoma Growth and Invasion Through the Notch/STAT3 Pathway
title_fullStr	RBM8A Promotes Glioblastoma Growth and Invasion Through the Notch/STAT3 Pathway
title_full_unstemmed	RBM8A Promotes Glioblastoma Growth and Invasion Through the Notch/STAT3 Pathway
title_sort	rbm8a promotes glioblastoma growth and invasion through the notch/stat3 pathway
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/2d2e58881778431fab63031040069905
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RBM8A Promotes Glioblastoma Growth and Invasion Through the Notch/STAT3 Pathway

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