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Inhibition of REST Suppresses Proliferation and Migration in Glioblastoma Cells

Glioblastoma (GBM) is the most common primary brain tumor, with poor prognosis and a lack of effective therapeutic options. The aberrant expression of transcription factor REST (repressor element 1-silencing transcription factor) had been reported in different kinds of tumors. However, the function...

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Autores principales: Zhang, Dianbao, Li, Ying, Wang, Rui, Li, Yunna, Shi, Ping, Kan, Zhoumi, Pang, Xining
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881490/
https://www.ncbi.nlm.nih.gov/pubmed/27153061
http://dx.doi.org/10.3390/ijms17050664
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author Zhang, Dianbao
Li, Ying
Wang, Rui
Li, Yunna
Shi, Ping
Kan, Zhoumi
Pang, Xining
author_facet Zhang, Dianbao
Li, Ying
Wang, Rui
Li, Yunna
Shi, Ping
Kan, Zhoumi
Pang, Xining
author_sort Zhang, Dianbao
collection PubMed
description Glioblastoma (GBM) is the most common primary brain tumor, with poor prognosis and a lack of effective therapeutic options. The aberrant expression of transcription factor REST (repressor element 1-silencing transcription factor) had been reported in different kinds of tumors. However, the function of REST and its mechanisms in GBM remain elusive. Here, REST expression was inhibited by siRNA silencing in U-87 and U-251 GBM cells. Then CCK-8 assay showed significantly decreased cell proliferation, and the inhibition of migration was verified by scratch wound healing assay and transwell assay. Using cell cycle analysis and Annexin V/PI straining assay, G1 phase cell cycle arrest was found to be a reason for the suppression of cell proliferation and migration upon REST silencing, while apoptosis was not affected by REST silencing. Further, the detection of REST-downstream genes involved in cytostasis and migration inhibition demonstrated that CCND1 and CCNE1 were reduced; CDK5R1, BBC3, EGR1, SLC25A4, PDCD7, MAPK11, MAPK12, FADD and DAXX were enhanced, among which BBC3 and DAXX were direct targets of REST, as verified by ChIP (chromatin immunoprecipitation) and Western blotting. These data suggested that REST is a master regulator that maintains GBM cells proliferation and migration, partly through regulating cell cycle by repressing downstream genes, which might represent a potential target for GBM therapy.
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spelling pubmed-48814902016-05-27 Inhibition of REST Suppresses Proliferation and Migration in Glioblastoma Cells Zhang, Dianbao Li, Ying Wang, Rui Li, Yunna Shi, Ping Kan, Zhoumi Pang, Xining Int J Mol Sci Article Glioblastoma (GBM) is the most common primary brain tumor, with poor prognosis and a lack of effective therapeutic options. The aberrant expression of transcription factor REST (repressor element 1-silencing transcription factor) had been reported in different kinds of tumors. However, the function of REST and its mechanisms in GBM remain elusive. Here, REST expression was inhibited by siRNA silencing in U-87 and U-251 GBM cells. Then CCK-8 assay showed significantly decreased cell proliferation, and the inhibition of migration was verified by scratch wound healing assay and transwell assay. Using cell cycle analysis and Annexin V/PI straining assay, G1 phase cell cycle arrest was found to be a reason for the suppression of cell proliferation and migration upon REST silencing, while apoptosis was not affected by REST silencing. Further, the detection of REST-downstream genes involved in cytostasis and migration inhibition demonstrated that CCND1 and CCNE1 were reduced; CDK5R1, BBC3, EGR1, SLC25A4, PDCD7, MAPK11, MAPK12, FADD and DAXX were enhanced, among which BBC3 and DAXX were direct targets of REST, as verified by ChIP (chromatin immunoprecipitation) and Western blotting. These data suggested that REST is a master regulator that maintains GBM cells proliferation and migration, partly through regulating cell cycle by repressing downstream genes, which might represent a potential target for GBM therapy. MDPI 2016-05-03 /pmc/articles/PMC4881490/ /pubmed/27153061 http://dx.doi.org/10.3390/ijms17050664 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhang, Dianbao
Li, Ying
Wang, Rui
Li, Yunna
Shi, Ping
Kan, Zhoumi
Pang, Xining
Inhibition of REST Suppresses Proliferation and Migration in Glioblastoma Cells
title Inhibition of REST Suppresses Proliferation and Migration in Glioblastoma Cells
title_full Inhibition of REST Suppresses Proliferation and Migration in Glioblastoma Cells
title_fullStr Inhibition of REST Suppresses Proliferation and Migration in Glioblastoma Cells
title_full_unstemmed Inhibition of REST Suppresses Proliferation and Migration in Glioblastoma Cells
title_short Inhibition of REST Suppresses Proliferation and Migration in Glioblastoma Cells
title_sort inhibition of rest suppresses proliferation and migration in glioblastoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881490/
https://www.ncbi.nlm.nih.gov/pubmed/27153061
http://dx.doi.org/10.3390/ijms17050664
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