title: Disrupted in schizophrenia 1 (DISC1) inhibits glioblastoma development by regulating mitochondria dynamics.
abstract: 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.
authors.affiliation: Institute of Basic Medical Sciences and Shaanxi key Laboratory of ischemic Cardiovascular Disease, Xi'an Medical University, Xi'an 710021, P. R. China.|Institute of Nano Biomedicine and Engineering, Department of Instrument Science and Engineering, Key Lab. for Thin Film and Microfabrication Technology of Ministry of Education, School of Electronic Information and Electronic Engineering, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.
authors.forename: Xingchun
authors.initials: X
authors.lastname: Gao
authors.affiliation: Institute of Basic Medical Sciences and Shaanxi key Laboratory of ischemic Cardiovascular Disease, Xi'an Medical University, Xi'an 710021, P. R. China.
authors.forename: Yajing
authors.initials: Y
authors.lastname: Mi
authors.affiliation: Institute of Basic Medical Sciences and Shaanxi key Laboratory of ischemic Cardiovascular Disease, Xi'an Medical University, Xi'an 710021, P. R. China.
authors.forename: Na
authors.initials: N
authors.lastname: Guo
authors.affiliation: Institute of Basic Medical Sciences and Shaanxi key Laboratory of ischemic Cardiovascular Disease, Xi'an Medical University, Xi'an 710021, P. R. China.
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Institute of Basic Medical Sciences and Shaanxi key Laboratory of ischemic Cardiovascular Disease, Xi'an Medical University, Xi'an 710021, P. R. China.
authors.forename: Fengrui
authors.initials: F
authors.lastname: Hu
authors.affiliation: Institute of Basic Medical Sciences and Shaanxi key Laboratory of ischemic Cardiovascular Disease, Xi'an Medical University, Xi'an 710021, P. R. China.
authors.forename: Dou
authors.initials: D
authors.lastname: Liu
authors.affiliation: Institute of Basic Medical Sciences and Shaanxi key Laboratory of ischemic Cardiovascular Disease, Xi'an Medical University, Xi'an 710021, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.affiliation: Institute of Basic Medical Sciences and Shaanxi key Laboratory of ischemic Cardiovascular Disease, Xi'an Medical University, Xi'an 710021, P. R. China.
authors.forename: Xingchun
authors.initials: X
authors.lastname: Gou
authors.affiliation: Institute of Basic Medical Sciences and Shaanxi key Laboratory of ischemic Cardiovascular Disease, Xi'an Medical University, Xi'an 710021, P. R. China.|Institute of Nano Biomedicine and Engineering, Department of Instrument Science and Engineering, Key Lab. for Thin Film and Microfabrication Technology of Ministry of Education, School of Electronic Information and Electronic Engineering, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.|National Centers for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.
authors.forename: Weilin
authors.initials: W
authors.lastname: Jin
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002465:Cell Movement; D049109:Cell Proliferation; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000502:physiology; D005909:Glioblastoma / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000502:physiology; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000502:physiology; D009361:Neoplasm Invasiveness; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: C412476:DISC1 protein, human; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D009419:Nerve Tissue Proteins; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins
keywords: DISC1; Drp1; glioblastoma; mitochondria dynamics; self-renewal