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Notch intracellular domain regulates glioblastoma proliferation through the Notch1 signaling pathway

Notch intracellular domain (NICD), also known as the activated form of Notch1 is closely associated with cell differentiation and tumor invasion. However, the role of NICD in glioblastoma (GBM) proliferation and the underlying regulatory mechanism remains unclear. The present study aimed to investig...

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Autores principales: Wang, Yixuan, Sun, Qian, Geng, Rongxin, Liu, Hao, Yuan, Fan'en, Xu, Yang, Qi, Yangzhi, Jiang, Hongxiang, Chen, Qianxue, Liu, Baohui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905607/
https://www.ncbi.nlm.nih.gov/pubmed/33732379
http://dx.doi.org/10.3892/ol.2021.12564
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author Wang, Yixuan
Sun, Qian
Geng, Rongxin
Liu, Hao
Yuan, Fan'en
Xu, Yang
Qi, Yangzhi
Jiang, Hongxiang
Chen, Qianxue
Liu, Baohui
author_facet Wang, Yixuan
Sun, Qian
Geng, Rongxin
Liu, Hao
Yuan, Fan'en
Xu, Yang
Qi, Yangzhi
Jiang, Hongxiang
Chen, Qianxue
Liu, Baohui
author_sort Wang, Yixuan
collection PubMed
description Notch intracellular domain (NICD), also known as the activated form of Notch1 is closely associated with cell differentiation and tumor invasion. However, the role of NICD in glioblastoma (GBM) proliferation and the underlying regulatory mechanism remains unclear. The present study aimed to investigate the expression of NICD and Notch1 downstream gene HES5 in human GBM and normal brain samples and to further detect the effect of NICD on human GBM cell proliferation. For this purpose, western blotting and immunohistochemical staining were performed to analyze the expression of NICD in human GBM tissues, while western blotting and reverse-transcription quantitative PCR experiments were used to analyze the expression of Hes5 in human GBM tissues. A Flag-NICD vector was used to overexpress NICD in U87 cells and compound E and small interfering (si) Notch1 were used to downregulate NICD. Cellular proliferation curves were generated and BrdU assays performed to evaluate the proliferation of U87 cells. The results demonstrated that compared with normal brain tissues, the level of NICD protein in human GBM tissues was upregulated and the protein and mRNA levels of Hes5 were also upregulated in GBM tissues indicating that the Notch1 signaling pathway is activated in GBM. Overexpression of NICD promoted the proliferation of U87 cells in vitro while downregulation of NICD by treatment with compound E or siNotch1 suppressed the proliferation of U87 cells in vitro. In conclusion, NICD was upregulated in human GBM and NICD promoted GBM proliferation via the Notch1 signaling pathway. NICD may be a potential diagnostic marker and therapeutic target for GBM treatment.
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spelling pubmed-79056072021-03-16 Notch intracellular domain regulates glioblastoma proliferation through the Notch1 signaling pathway Wang, Yixuan Sun, Qian Geng, Rongxin Liu, Hao Yuan, Fan'en Xu, Yang Qi, Yangzhi Jiang, Hongxiang Chen, Qianxue Liu, Baohui Oncol Lett Articles Notch intracellular domain (NICD), also known as the activated form of Notch1 is closely associated with cell differentiation and tumor invasion. However, the role of NICD in glioblastoma (GBM) proliferation and the underlying regulatory mechanism remains unclear. The present study aimed to investigate the expression of NICD and Notch1 downstream gene HES5 in human GBM and normal brain samples and to further detect the effect of NICD on human GBM cell proliferation. For this purpose, western blotting and immunohistochemical staining were performed to analyze the expression of NICD in human GBM tissues, while western blotting and reverse-transcription quantitative PCR experiments were used to analyze the expression of Hes5 in human GBM tissues. A Flag-NICD vector was used to overexpress NICD in U87 cells and compound E and small interfering (si) Notch1 were used to downregulate NICD. Cellular proliferation curves were generated and BrdU assays performed to evaluate the proliferation of U87 cells. The results demonstrated that compared with normal brain tissues, the level of NICD protein in human GBM tissues was upregulated and the protein and mRNA levels of Hes5 were also upregulated in GBM tissues indicating that the Notch1 signaling pathway is activated in GBM. Overexpression of NICD promoted the proliferation of U87 cells in vitro while downregulation of NICD by treatment with compound E or siNotch1 suppressed the proliferation of U87 cells in vitro. In conclusion, NICD was upregulated in human GBM and NICD promoted GBM proliferation via the Notch1 signaling pathway. NICD may be a potential diagnostic marker and therapeutic target for GBM treatment. D.A. Spandidos 2021-04 2021-02-19 /pmc/articles/PMC7905607/ /pubmed/33732379 http://dx.doi.org/10.3892/ol.2021.12564 Text en Copyright: © Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , 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 Articles
Wang, Yixuan
Sun, Qian
Geng, Rongxin
Liu, Hao
Yuan, Fan'en
Xu, Yang
Qi, Yangzhi
Jiang, Hongxiang
Chen, Qianxue
Liu, Baohui
Notch intracellular domain regulates glioblastoma proliferation through the Notch1 signaling pathway
title Notch intracellular domain regulates glioblastoma proliferation through the Notch1 signaling pathway
title_full Notch intracellular domain regulates glioblastoma proliferation through the Notch1 signaling pathway
title_fullStr Notch intracellular domain regulates glioblastoma proliferation through the Notch1 signaling pathway
title_full_unstemmed Notch intracellular domain regulates glioblastoma proliferation through the Notch1 signaling pathway
title_short Notch intracellular domain regulates glioblastoma proliferation through the Notch1 signaling pathway
title_sort notch intracellular domain regulates glioblastoma proliferation through the notch1 signaling pathway
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905607/
https://www.ncbi.nlm.nih.gov/pubmed/33732379
http://dx.doi.org/10.3892/ol.2021.12564
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