Modulation of MicroRNA-194 and cell migration by HER2-targeting trastuzumab in breast cancer

Detalhes bibliográficos
Autor(a) principal: Le, Xiao-Fen
Data de Publicação: 2012
Outros Autores: Almeida, Maria Inês, Mao, Weiqu, Spizzo, Riccardo, Rossi, Simona, Nicoloso, Milena S., Zhang, Shu, Wu, Yun, Calin, George A., Bast, Robert C.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/1822/24117
Resumo: Conceived and designed the experiments: XFL GAC RCB. Performed the experiments: XFL MIA WM RS MSN SZ. Analyzed the data: XFL SR. Contributed reagents/materials/analysis tools: YW GAC. Wrote the paper: XFL RCB.
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spelling Modulation of MicroRNA-194 and cell migration by HER2-targeting trastuzumab in breast cancerScience & TechnologyConceived and designed the experiments: XFL GAC RCB. Performed the experiments: XFL MIA WM RS MSN SZ. Analyzed the data: XFL SR. Contributed reagents/materials/analysis tools: YW GAC. Wrote the paper: XFL RCB.Trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of the HER2 oncoprotein, can effectively target HER2-positive breast cancer through several mechanisms. Although the effects of trastuzumab on cancer cell proliferation, angiogenesis and apoptosis have been investigated in depth, the effect of trastuzumab on microRNA (miRNA) has not been extensively studied. We have performed miRNA microarray profiling before and after trastuzumab treatment in SKBr3 and BT474 human breast cancer cells that overexpress HER2. We found that trastuzumab treatment of SKBr3 cells significantly decreased five miRNAs and increased three others, whereas treatment of BT474 cells significantly decreased two miRNAs and increased nine. The only change in miRNA expression observed in both cell lines following trastuzumab treatment was upregulation of miRNA-194 (miR-194) that was further validated in vitro and in vivo. Forced expression of miR-194 in breast cancer cells that overexpress HER2 produced no effect on apoptosis, modest inhibition of proliferation, significant inhibition of cell migration/invasion in vitro and significant inhibition of xenograft growth in vivo. Conversely, knockdown of miR-194 promoted cell migration. Increased miR-194 expression markedly reduced levels of the cytoskeletal protein talin2 and specifically inhibited luciferase reporter activity of a talin2 wild-type 39-untranslated region, but not that of a mutant reporter, indicating that talin2 is a direct downstream target of miR-194. Trastuzumab treatment inhibited breast cancer cell migration and reduced talin2 expression in vitro and in vivo. Knockdown of talin2 inhibited cell migration/invasion. Knockdown of trastuzumab-induced miR-194 expression with a miR-194 inhibitor compromised trastuzumab-inhibited cell migration in HER2-overexpressing breast cancer cells. Consequently, trastuzumab treatment upregulates miR-194 expression and may exert its cell migration-inhibitory effect through miR-194-mediated downregulation of cytoskeleton protein talin2 in HER2-overexpressing human breast cancer cells.This work was supported by the Anne and Henry Zarrow Foundation, kind gifts from Stuart and Gaye Lynn Zarrow and from Mrs. Delores Wilkenfeld, the Laura and John Arnold Foundation, the RGK Foundation, and the MD Anderson NCI CCSG P30 CA16672. G.A.C. is supported as a Fellow at the University of Texas MD Anderson Research Trust, as a University of Texas System Regents Research Scholar and by the CLL Global Research Foundation.Public Library of ScienceUniversidade do MinhoLe, Xiao-FenAlmeida, Maria InêsMao, WeiquSpizzo, RiccardoRossi, SimonaNicoloso, Milena S.Zhang, ShuWu, YunCalin, George A.Bast, Robert C.2012-072012-07-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/24117engLe X-F, Almeida MI, Mao W, Spizzo R, Rossi S, et al. (2012) Modulation of MicroRNA-194 and Cell Migration by HER2-Targeting Trastuzumab in Breast Cancer. PLoS ONE 7(7): e41170. doi:10.1371/journal.pone.00411701932-620310.1371/journal.pone.004117022829924http://dx.plos.org/10.1371/journal.pone.0041170info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:19:57Zoai:repositorium.sdum.uminho.pt:1822/24117Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:12:59.922926Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Modulation of MicroRNA-194 and cell migration by HER2-targeting trastuzumab in breast cancer
title Modulation of MicroRNA-194 and cell migration by HER2-targeting trastuzumab in breast cancer
spellingShingle Modulation of MicroRNA-194 and cell migration by HER2-targeting trastuzumab in breast cancer
Le, Xiao-Fen
Science & Technology
title_short Modulation of MicroRNA-194 and cell migration by HER2-targeting trastuzumab in breast cancer
title_full Modulation of MicroRNA-194 and cell migration by HER2-targeting trastuzumab in breast cancer
title_fullStr Modulation of MicroRNA-194 and cell migration by HER2-targeting trastuzumab in breast cancer
title_full_unstemmed Modulation of MicroRNA-194 and cell migration by HER2-targeting trastuzumab in breast cancer
title_sort Modulation of MicroRNA-194 and cell migration by HER2-targeting trastuzumab in breast cancer
author Le, Xiao-Fen
author_facet Le, Xiao-Fen
Almeida, Maria Inês
Mao, Weiqu
Spizzo, Riccardo
Rossi, Simona
Nicoloso, Milena S.
Zhang, Shu
Wu, Yun
Calin, George A.
Bast, Robert C.
author_role author
author2 Almeida, Maria Inês
Mao, Weiqu
Spizzo, Riccardo
Rossi, Simona
Nicoloso, Milena S.
Zhang, Shu
Wu, Yun
Calin, George A.
Bast, Robert C.
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Le, Xiao-Fen
Almeida, Maria Inês
Mao, Weiqu
Spizzo, Riccardo
Rossi, Simona
Nicoloso, Milena S.
Zhang, Shu
Wu, Yun
Calin, George A.
Bast, Robert C.
dc.subject.por.fl_str_mv Science & Technology
topic Science & Technology
description Conceived and designed the experiments: XFL GAC RCB. Performed the experiments: XFL MIA WM RS MSN SZ. Analyzed the data: XFL SR. Contributed reagents/materials/analysis tools: YW GAC. Wrote the paper: XFL RCB.
publishDate 2012
dc.date.none.fl_str_mv 2012-07
2012-07-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1822/24117
url http://hdl.handle.net/1822/24117
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Le X-F, Almeida MI, Mao W, Spizzo R, Rossi S, et al. (2012) Modulation of MicroRNA-194 and Cell Migration by HER2-Targeting Trastuzumab in Breast Cancer. PLoS ONE 7(7): e41170. doi:10.1371/journal.pone.0041170
1932-6203
10.1371/journal.pone.0041170
22829924
http://dx.plos.org/10.1371/journal.pone.0041170
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dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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