Knockdown of E2f1 by RNA interference impairs proliferation of rat cells in vitro
Autor(a) principal: | |
---|---|
Data de Publicação: | 2010 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Genetics and Molecular Biology |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572010000100005 |
Resumo: | E2F1 plays a key role in cell-cycle regulation in mammals, since its transcription factor activity controls genes required for DNA synthesis and apoptosis. E2F1 deregulation is a common feature among different tumor types and can be a major cause of cell proliferation. Thus, blocking E2F1 expression by RNA interference represents a promising therapeutic approach. In this study, the introduction of specific short hairpin RNAs (shRNAs) reduced E2f1 expression by up to 77%, and impaired rat glioma cell proliferation by approximately 70%, as compared to control cells. Furthermore, we investigated the expression of E2f1 target genes, Cyclin A and Cyclin E. Cyclin A was found to be down-regulated, whereas Cyclin E had similar expression to control cells, indicating that gene(s) other than E2f1 control its transcription. Other E2f family members, E2f2 and E2f3, which have been classified in the same subgroup of transcriptional activators, were also analyzed. Expression of both E2f2 and E2f3 was similar to control cells, showing no cross-inactivation or up-regulation to compensate for the absence of E2f1. Nevertheless, their expression was insufficient to maintain the initial proliferation potential. Taken together, our results suggest that shE2f1 is a promising therapy to control tumor cell proliferation. |
id |
SBG-1_dce563061cb3d496ec76fc69a107ac75 |
---|---|
oai_identifier_str |
oai:scielo:S1415-47572010000100005 |
network_acronym_str |
SBG-1 |
network_name_str |
Genetics and Molecular Biology |
repository_id_str |
|
spelling |
Knockdown of E2f1 by RNA interference impairs proliferation of rat cells in vitroRNAishRNAE2F1proliferationcancerE2F1 plays a key role in cell-cycle regulation in mammals, since its transcription factor activity controls genes required for DNA synthesis and apoptosis. E2F1 deregulation is a common feature among different tumor types and can be a major cause of cell proliferation. Thus, blocking E2F1 expression by RNA interference represents a promising therapeutic approach. In this study, the introduction of specific short hairpin RNAs (shRNAs) reduced E2f1 expression by up to 77%, and impaired rat glioma cell proliferation by approximately 70%, as compared to control cells. Furthermore, we investigated the expression of E2f1 target genes, Cyclin A and Cyclin E. Cyclin A was found to be down-regulated, whereas Cyclin E had similar expression to control cells, indicating that gene(s) other than E2f1 control its transcription. Other E2f family members, E2f2 and E2f3, which have been classified in the same subgroup of transcriptional activators, were also analyzed. Expression of both E2f2 and E2f3 was similar to control cells, showing no cross-inactivation or up-regulation to compensate for the absence of E2f1. Nevertheless, their expression was insufficient to maintain the initial proliferation potential. Taken together, our results suggest that shE2f1 is a promising therapy to control tumor cell proliferation.Sociedade Brasileira de Genética2010-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572010000100005Genetics and Molecular Biology v.33 n.1 2010reponame:Genetics and Molecular Biologyinstname:Sociedade Brasileira de Genética (SBG)instacron:SBG10.1590/S1415-47572009005000104info:eu-repo/semantics/openAccessVasques,Luciana dos ReisPujiz,Regiane SimoniStrauss,Bryan EricKrieger,José Eduardoeng2010-02-12T00:00:00Zoai:scielo:S1415-47572010000100005Revistahttp://www.gmb.org.br/ONGhttps://old.scielo.br/oai/scielo-oai.php||editor@gmb.org.br1678-46851415-4757opendoar:2010-02-12T00:00Genetics and Molecular Biology - Sociedade Brasileira de Genética (SBG)false |
dc.title.none.fl_str_mv |
Knockdown of E2f1 by RNA interference impairs proliferation of rat cells in vitro |
title |
Knockdown of E2f1 by RNA interference impairs proliferation of rat cells in vitro |
spellingShingle |
Knockdown of E2f1 by RNA interference impairs proliferation of rat cells in vitro Vasques,Luciana dos Reis RNAi shRNA E2F1 proliferation cancer |
title_short |
Knockdown of E2f1 by RNA interference impairs proliferation of rat cells in vitro |
title_full |
Knockdown of E2f1 by RNA interference impairs proliferation of rat cells in vitro |
title_fullStr |
Knockdown of E2f1 by RNA interference impairs proliferation of rat cells in vitro |
title_full_unstemmed |
Knockdown of E2f1 by RNA interference impairs proliferation of rat cells in vitro |
title_sort |
Knockdown of E2f1 by RNA interference impairs proliferation of rat cells in vitro |
author |
Vasques,Luciana dos Reis |
author_facet |
Vasques,Luciana dos Reis Pujiz,Regiane Simoni Strauss,Bryan Eric Krieger,José Eduardo |
author_role |
author |
author2 |
Pujiz,Regiane Simoni Strauss,Bryan Eric Krieger,José Eduardo |
author2_role |
author author author |
dc.contributor.author.fl_str_mv |
Vasques,Luciana dos Reis Pujiz,Regiane Simoni Strauss,Bryan Eric Krieger,José Eduardo |
dc.subject.por.fl_str_mv |
RNAi shRNA E2F1 proliferation cancer |
topic |
RNAi shRNA E2F1 proliferation cancer |
description |
E2F1 plays a key role in cell-cycle regulation in mammals, since its transcription factor activity controls genes required for DNA synthesis and apoptosis. E2F1 deregulation is a common feature among different tumor types and can be a major cause of cell proliferation. Thus, blocking E2F1 expression by RNA interference represents a promising therapeutic approach. In this study, the introduction of specific short hairpin RNAs (shRNAs) reduced E2f1 expression by up to 77%, and impaired rat glioma cell proliferation by approximately 70%, as compared to control cells. Furthermore, we investigated the expression of E2f1 target genes, Cyclin A and Cyclin E. Cyclin A was found to be down-regulated, whereas Cyclin E had similar expression to control cells, indicating that gene(s) other than E2f1 control its transcription. Other E2f family members, E2f2 and E2f3, which have been classified in the same subgroup of transcriptional activators, were also analyzed. Expression of both E2f2 and E2f3 was similar to control cells, showing no cross-inactivation or up-regulation to compensate for the absence of E2f1. Nevertheless, their expression was insufficient to maintain the initial proliferation potential. Taken together, our results suggest that shE2f1 is a promising therapy to control tumor cell proliferation. |
publishDate |
2010 |
dc.date.none.fl_str_mv |
2010-01-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572010000100005 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572010000100005 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/S1415-47572009005000104 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Sociedade Brasileira de Genética |
publisher.none.fl_str_mv |
Sociedade Brasileira de Genética |
dc.source.none.fl_str_mv |
Genetics and Molecular Biology v.33 n.1 2010 reponame:Genetics and Molecular Biology instname:Sociedade Brasileira de Genética (SBG) instacron:SBG |
instname_str |
Sociedade Brasileira de Genética (SBG) |
instacron_str |
SBG |
institution |
SBG |
reponame_str |
Genetics and Molecular Biology |
collection |
Genetics and Molecular Biology |
repository.name.fl_str_mv |
Genetics and Molecular Biology - Sociedade Brasileira de Genética (SBG) |
repository.mail.fl_str_mv |
||editor@gmb.org.br |
_version_ |
1752122382426832896 |