Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Gao, Xingchun, Mi, Yajing, Guo, Na, Hu, Zhifang, Hu, Fengrui, liu, Dou, Gao, Lei, Gou, Xingchun, Jin, Weilin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
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
_version_ 1782514550315155456
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
work_keys_str_mv AT gaoxingchun disruptedinschizophrenia1disc1inhibitsglioblastomadevelopmentbyregulatingmitochondriadynamics
AT miyajing disruptedinschizophrenia1disc1inhibitsglioblastomadevelopmentbyregulatingmitochondriadynamics
AT guona disruptedinschizophrenia1disc1inhibitsglioblastomadevelopmentbyregulatingmitochondriadynamics
AT huzhifang disruptedinschizophrenia1disc1inhibitsglioblastomadevelopmentbyregulatingmitochondriadynamics
AT hufengrui disruptedinschizophrenia1disc1inhibitsglioblastomadevelopmentbyregulatingmitochondriadynamics
AT liudou disruptedinschizophrenia1disc1inhibitsglioblastomadevelopmentbyregulatingmitochondriadynamics
AT gaolei disruptedinschizophrenia1disc1inhibitsglioblastomadevelopmentbyregulatingmitochondriadynamics
AT gouxingchun disruptedinschizophrenia1disc1inhibitsglioblastomadevelopmentbyregulatingmitochondriadynamics
AT jinweilin disruptedinschizophrenia1disc1inhibitsglioblastomadevelopmentbyregulatingmitochondriadynamics