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Disrupted in schizophrenia 1 (DISC1) inhibits glioblastoma development by regulating mitochondria dynamics
Glioblastoma(GBM) is one of the most common and aggressive malignant primary tumors of the central nervous system and mitochondria have been proposed to participate in GBM tumorigenesis. Previous studies have identified a potential role of Disrupted in Schizophrenia 1 (DISC1), a multi-compartmentali...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349889/ https://www.ncbi.nlm.nih.gov/pubmed/27852062 http://dx.doi.org/10.18632/oncotarget.13290 |
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author | Gao, Xingchun Mi, Yajing Guo, Na Hu, Zhifang Hu, Fengrui liu, Dou Gao, Lei Gou, Xingchun Jin, Weilin |
author_facet | Gao, Xingchun Mi, Yajing Guo, Na Hu, Zhifang Hu, Fengrui liu, Dou Gao, Lei Gou, Xingchun Jin, Weilin |
author_sort | Gao, Xingchun |
collection | PubMed |
description | Glioblastoma(GBM) is one of the most common and aggressive malignant primary tumors of the central nervous system and mitochondria have been proposed to participate in GBM tumorigenesis. Previous studies have identified a potential role of Disrupted in Schizophrenia 1 (DISC1), a multi-compartmentalized protein, in mitochondria. But whether DISC1 could regulate GBM tumorigenesis via mitochondria is still unknown. We determined the expression level of DISC1 by both bioinformatics analysis and tissue analysis, and found that DISC1 was highly expressed in GBM. Knocking down of DISC1 by shRNA in GBM cells significantly inhibited cell proliferation both in vitro and in vivo. In addition, down-regulation of DISC1 decreased cell migration and invasion of GBM and self renewal capacity of glioblastoma stem-like cells. Furthermore, multiple independent rings or spheres could be observed in mitochondria in GBM depleted of DISC1, while normal filamentous morphology was observed in control cells, demonstrating that DISC1 affected the mitochondrial dynamic. Dynamin-related protein 1 (Drp1) was reported to contribute to mitochondrial dynamic regulation and influence glioma cells proliferation and invasion by RHOA/ ROCK1 pathway. Our data showed a significant decrease of Drp1 both in mRNA and protein level in GBM lack of DISC1, indicating that DISC1 maybe affect the mitochondrial dynamic by regulating Drp1. Taken together, our findings reveal that DISC1 affects glioblastoma cell development via mitochondria dynamics partly by down regulation of Drp1. |
format | Online Article Text |
id | pubmed-5349889 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53498892017-04-06 Disrupted in schizophrenia 1 (DISC1) inhibits glioblastoma development by regulating mitochondria dynamics Gao, Xingchun Mi, Yajing Guo, Na Hu, Zhifang Hu, Fengrui liu, Dou Gao, Lei Gou, Xingchun Jin, Weilin Oncotarget Research Paper Glioblastoma(GBM) is one of the most common and aggressive malignant primary tumors of the central nervous system and mitochondria have been proposed to participate in GBM tumorigenesis. Previous studies have identified a potential role of Disrupted in Schizophrenia 1 (DISC1), a multi-compartmentalized protein, in mitochondria. But whether DISC1 could regulate GBM tumorigenesis via mitochondria is still unknown. We determined the expression level of DISC1 by both bioinformatics analysis and tissue analysis, and found that DISC1 was highly expressed in GBM. Knocking down of DISC1 by shRNA in GBM cells significantly inhibited cell proliferation both in vitro and in vivo. In addition, down-regulation of DISC1 decreased cell migration and invasion of GBM and self renewal capacity of glioblastoma stem-like cells. Furthermore, multiple independent rings or spheres could be observed in mitochondria in GBM depleted of DISC1, while normal filamentous morphology was observed in control cells, demonstrating that DISC1 affected the mitochondrial dynamic. Dynamin-related protein 1 (Drp1) was reported to contribute to mitochondrial dynamic regulation and influence glioma cells proliferation and invasion by RHOA/ ROCK1 pathway. Our data showed a significant decrease of Drp1 both in mRNA and protein level in GBM lack of DISC1, indicating that DISC1 maybe affect the mitochondrial dynamic by regulating Drp1. Taken together, our findings reveal that DISC1 affects glioblastoma cell development via mitochondria dynamics partly by down regulation of Drp1. Impact Journals LLC 2016-11-11 /pmc/articles/PMC5349889/ /pubmed/27852062 http://dx.doi.org/10.18632/oncotarget.13290 Text en Copyright: © 2016 Gao et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Gao, Xingchun Mi, Yajing Guo, Na Hu, Zhifang Hu, Fengrui liu, Dou Gao, Lei Gou, Xingchun Jin, Weilin Disrupted in schizophrenia 1 (DISC1) inhibits glioblastoma development by regulating mitochondria dynamics |
title | Disrupted in schizophrenia 1 (DISC1) inhibits glioblastoma development by regulating mitochondria dynamics |
title_full | Disrupted in schizophrenia 1 (DISC1) inhibits glioblastoma development by regulating mitochondria dynamics |
title_fullStr | Disrupted in schizophrenia 1 (DISC1) inhibits glioblastoma development by regulating mitochondria dynamics |
title_full_unstemmed | Disrupted in schizophrenia 1 (DISC1) inhibits glioblastoma development by regulating mitochondria dynamics |
title_short | Disrupted in schizophrenia 1 (DISC1) inhibits glioblastoma development by regulating mitochondria dynamics |
title_sort | disrupted in schizophrenia 1 (disc1) inhibits glioblastoma development by regulating mitochondria dynamics |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349889/ https://www.ncbi.nlm.nih.gov/pubmed/27852062 http://dx.doi.org/10.18632/oncotarget.13290 |
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