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Glioma stem cells-derived exosomes promote the angiogenic ability of endothelial cells through miR-21/VEGF signal

Glioma stem cells (GSCs) play an important role in glioblastoma prognosis. Exosomes (EXs) mediate cell communication by delivering microRNAs (miRs). Glioblastoma has a high level of miR-21 which could upregulate vascular endothelial growth factor (VEGF) expression. We hypothesized GSC-EXs can promot...

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Detalles Bibliográficos
Autores principales: Sun, Xu, Ma, Xiaotang, Wang, Jinju, Zhao, Yuhui, Wang, Yue, Bihl, Ji C., Chen, Yanfang, Jiang, Chuanlu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482644/
https://www.ncbi.nlm.nih.gov/pubmed/28410224
http://dx.doi.org/10.18632/oncotarget.16661
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author Sun, Xu
Ma, Xiaotang
Wang, Jinju
Zhao, Yuhui
Wang, Yue
Bihl, Ji C.
Chen, Yanfang
Jiang, Chuanlu
author_facet Sun, Xu
Ma, Xiaotang
Wang, Jinju
Zhao, Yuhui
Wang, Yue
Bihl, Ji C.
Chen, Yanfang
Jiang, Chuanlu
author_sort Sun, Xu
collection PubMed
description Glioma stem cells (GSCs) play an important role in glioblastoma prognosis. Exosomes (EXs) mediate cell communication by delivering microRNAs (miRs). Glioblastoma has a high level of miR-21 which could upregulate vascular endothelial growth factor (VEGF) expression. We hypothesized GSC-EXs can promote the angiogenic ability of endothelial cells (ECs) through miR-21/VEGF signal. GSCs were isolated from U-251 cells with stem cell marker CD133. GSCs transfected without or with scramble or miR-21 mimics were used to produce GSC-(EXs)con, GSC-EXs(sc) and GSC-EXs(miR-21). Human brain ECs were co-cultured with vehicle, GSC-EXs(con), GSC-EXs(sc) or GSC-EXs(miR-21) plus VEGF siRNAs (siRNA(VEGF)). After 24 hours, the angiogenic abilities of ECs were evaluated. The levels of miR-21, VEGF and p-Flk1/VEGFR2 were determined. Results showed: 1) Over 90% of purified GSCs expressed CD133; 2) The levels of miR-21 and VEGF in GSCs and GSC-EXs were up-regulated by miR-21 mimic transfection; 3) Compared to GSC-EXs(con) or GSC-EXs(sc), GSC-EXs(miR-21) were more effective in elevating the levels of miR-21 and VEGF, and the ratio of p-Flk1/VEGFR2 in ECs; 4) GSC-EXsmiR-21 were more effective in promoting the angiogenic ability of ECs than GSC-EXs(con) or GSC-EXs(sc), which were remarkably reduced by siRNA(VEGF) pretreatment. In conclusion, GSC-EXs can promote the angiogenic ability of ECs by stimulating miR-21/VEGF/VEGFR2 signal pathway.
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spelling pubmed-54826442017-06-27 Glioma stem cells-derived exosomes promote the angiogenic ability of endothelial cells through miR-21/VEGF signal Sun, Xu Ma, Xiaotang Wang, Jinju Zhao, Yuhui Wang, Yue Bihl, Ji C. Chen, Yanfang Jiang, Chuanlu Oncotarget Research Paper Glioma stem cells (GSCs) play an important role in glioblastoma prognosis. Exosomes (EXs) mediate cell communication by delivering microRNAs (miRs). Glioblastoma has a high level of miR-21 which could upregulate vascular endothelial growth factor (VEGF) expression. We hypothesized GSC-EXs can promote the angiogenic ability of endothelial cells (ECs) through miR-21/VEGF signal. GSCs were isolated from U-251 cells with stem cell marker CD133. GSCs transfected without or with scramble or miR-21 mimics were used to produce GSC-(EXs)con, GSC-EXs(sc) and GSC-EXs(miR-21). Human brain ECs were co-cultured with vehicle, GSC-EXs(con), GSC-EXs(sc) or GSC-EXs(miR-21) plus VEGF siRNAs (siRNA(VEGF)). After 24 hours, the angiogenic abilities of ECs were evaluated. The levels of miR-21, VEGF and p-Flk1/VEGFR2 were determined. Results showed: 1) Over 90% of purified GSCs expressed CD133; 2) The levels of miR-21 and VEGF in GSCs and GSC-EXs were up-regulated by miR-21 mimic transfection; 3) Compared to GSC-EXs(con) or GSC-EXs(sc), GSC-EXs(miR-21) were more effective in elevating the levels of miR-21 and VEGF, and the ratio of p-Flk1/VEGFR2 in ECs; 4) GSC-EXsmiR-21 were more effective in promoting the angiogenic ability of ECs than GSC-EXs(con) or GSC-EXs(sc), which were remarkably reduced by siRNA(VEGF) pretreatment. In conclusion, GSC-EXs can promote the angiogenic ability of ECs by stimulating miR-21/VEGF/VEGFR2 signal pathway. Impact Journals LLC 2017-03-29 /pmc/articles/PMC5482644/ /pubmed/28410224 http://dx.doi.org/10.18632/oncotarget.16661 Text en Copyright: © 2017 Sun et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Sun, Xu
Ma, Xiaotang
Wang, Jinju
Zhao, Yuhui
Wang, Yue
Bihl, Ji C.
Chen, Yanfang
Jiang, Chuanlu
Glioma stem cells-derived exosomes promote the angiogenic ability of endothelial cells through miR-21/VEGF signal
title Glioma stem cells-derived exosomes promote the angiogenic ability of endothelial cells through miR-21/VEGF signal
title_full Glioma stem cells-derived exosomes promote the angiogenic ability of endothelial cells through miR-21/VEGF signal
title_fullStr Glioma stem cells-derived exosomes promote the angiogenic ability of endothelial cells through miR-21/VEGF signal
title_full_unstemmed Glioma stem cells-derived exosomes promote the angiogenic ability of endothelial cells through miR-21/VEGF signal
title_short Glioma stem cells-derived exosomes promote the angiogenic ability of endothelial cells through miR-21/VEGF signal
title_sort glioma stem cells-derived exosomes promote the angiogenic ability of endothelial cells through mir-21/vegf signal
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482644/
https://www.ncbi.nlm.nih.gov/pubmed/28410224
http://dx.doi.org/10.18632/oncotarget.16661
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