Genome-wide RNAi screening identifies genes inhibiting the migration of glioblastoma cells.
Glioblastoma Multiforme (GBM) cells are highly invasive, infiltrating into the surrounding normal brain tissue, making it impossible to completely eradicate GBM tumors by surgery or radiation. Increasing evidence also shows that these migratory cells are highly resistant to cytotoxic reagents, but d...
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doaj-e4d14514aa7546d6be6103f268d606512020-11-25T01:30:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0184e6191510.1371/journal.pone.0061915Genome-wide RNAi screening identifies genes inhibiting the migration of glioblastoma cells.Jian YangJing FanYing LiFuhai LiPeikai ChenYubo FanXiaofeng XiaStephen T WongGlioblastoma Multiforme (GBM) cells are highly invasive, infiltrating into the surrounding normal brain tissue, making it impossible to completely eradicate GBM tumors by surgery or radiation. Increasing evidence also shows that these migratory cells are highly resistant to cytotoxic reagents, but decreasing their migratory capability can re-sensitize them to chemotherapy. These evidences suggest that the migratory cell population may serve as a better therapeutic target for more effective treatment of GBM. In order to understand the regulatory mechanism underlying the motile phenotype, we carried out a genome-wide RNAi screen for genes inhibiting the migration of GBM cells. The screening identified a total of twenty-five primary hits; seven of them were confirmed by secondary screening. Further study showed that three of the genes, FLNA, KHSRP and HCFC1, also functioned in vivo, and knocking them down caused multifocal tumor in a mouse model. Interestingly, two genes, KHSRP and HCFC1, were also found to be correlated with the clinical outcome of GBM patients. These two genes have not been previously associated with cell migration.http://europepmc.org/articles/PMC3625150?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jian Yang Jing Fan Ying Li Fuhai Li Peikai Chen Yubo Fan Xiaofeng Xia Stephen T Wong |
spellingShingle |
Jian Yang Jing Fan Ying Li Fuhai Li Peikai Chen Yubo Fan Xiaofeng Xia Stephen T Wong Genome-wide RNAi screening identifies genes inhibiting the migration of glioblastoma cells. PLoS ONE |
author_facet |
Jian Yang Jing Fan Ying Li Fuhai Li Peikai Chen Yubo Fan Xiaofeng Xia Stephen T Wong |
author_sort |
Jian Yang |
title |
Genome-wide RNAi screening identifies genes inhibiting the migration of glioblastoma cells. |
title_short |
Genome-wide RNAi screening identifies genes inhibiting the migration of glioblastoma cells. |
title_full |
Genome-wide RNAi screening identifies genes inhibiting the migration of glioblastoma cells. |
title_fullStr |
Genome-wide RNAi screening identifies genes inhibiting the migration of glioblastoma cells. |
title_full_unstemmed |
Genome-wide RNAi screening identifies genes inhibiting the migration of glioblastoma cells. |
title_sort |
genome-wide rnai screening identifies genes inhibiting the migration of glioblastoma cells. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
Glioblastoma Multiforme (GBM) cells are highly invasive, infiltrating into the surrounding normal brain tissue, making it impossible to completely eradicate GBM tumors by surgery or radiation. Increasing evidence also shows that these migratory cells are highly resistant to cytotoxic reagents, but decreasing their migratory capability can re-sensitize them to chemotherapy. These evidences suggest that the migratory cell population may serve as a better therapeutic target for more effective treatment of GBM. In order to understand the regulatory mechanism underlying the motile phenotype, we carried out a genome-wide RNAi screen for genes inhibiting the migration of GBM cells. The screening identified a total of twenty-five primary hits; seven of them were confirmed by secondary screening. Further study showed that three of the genes, FLNA, KHSRP and HCFC1, also functioned in vivo, and knocking them down caused multifocal tumor in a mouse model. Interestingly, two genes, KHSRP and HCFC1, were also found to be correlated with the clinical outcome of GBM patients. These two genes have not been previously associated with cell migration. |
url |
http://europepmc.org/articles/PMC3625150?pdf=render |
work_keys_str_mv |
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