Cyclooxygenase-2 is a target of microRNA-16 in human hepatoma cells

Autores
Agra Andrieu, Noelia; Motiño, Omar; Mayoral, Rafael; Llorente Izquierdo, Cristina; Fernández Alvarez, Ana Julia; Boscá, Lisardo; Casado, Marta; Martin Sanz, Paloma
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cyclooxygenase-2 (COX-2) expression has been detected in human hepatoma cell lines and in human hepatocellular carcinoma (HCC); however, the contribution of COX-2 to the development of HCC remains controversial. COX-2 expression is higher in the non-tumoral tissue and inversely correlates with the differentiation grade of the tumor. COX-2 expression depends on the interplay between different cellular pathways involving both transcriptional and post-transcriptional regulation. The aim of this work was to assess whether COX-2 could be regulated by microRNAs in human hepatoma cell lines and in human HCC specimens since these molecules contribute to the regulation of genes implicated in cell growth and differentiation. Our results show that miR-16 silences COX-2 expression in hepatoma cells by two mechanisms: a) by binding directly to the microRNA response element (MRE) in the COX-2 3'-UTR promoting translational suppression of COX-2 mRNA; b) by decreasing the levels of the RNA-binding protein Human Antigen R (HuR). Furthermore, ectopic expression of miR-16 inhibits cell proliferation, promotes cell apoptosis and suppresses the ability of hepatoma cells to develop tumors in nude mice, partially through targeting COX-2. Moreover a reduced miR-16 expression tends to correlate to high levels of COX-2 protein in liver from patients affected by HCC. Our data show an important role for miR-16 as a post-transcriptional regulator of COX-2 in HCC and suggest the potential therapeutic application of miR-16 in those HCC with a high COX-2 expression.
Fil: Agra Andrieu, Noelia. Consejo Superior de Investigaciones Cientificas; España
Fil: Motiño, Omar. Consejo Superior de Investigaciones Cientificas; España
Fil: Mayoral, Rafael. Consejo Superior de Investigaciones Cientificas; España
Fil: Llorente Izquierdo, Cristina. Consejo Superior de Investigaciones Cientificas; España
Fil: Fernández Alvarez, Ana Julia. Consejo Superior de Investigaciones Cientificas; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Boscá, Lisardo. Consejo Superior de Investigaciones Cientificas; España
Fil: Casado, Marta. Consejo Superior de Investigaciones Cientificas; España
Fil: Martin Sanz, Paloma. Consejo Superior de Investigaciones Cientificas; España
Materia
Cycloxigenase
Epigenetics
miRNA
Cancer
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/20865
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/20865
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Cyclooxygenase-2 is a target of microRNA-16 in human hepatoma cellsAgra Andrieu, NoeliaMotiño, OmarMayoral, RafaelLlorente Izquierdo, CristinaFernández Alvarez, Ana JuliaBoscá, LisardoCasado, MartaMartin Sanz, PalomaCycloxigenaseEpigeneticsmiRNACancerhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Cyclooxygenase-2 (COX-2) expression has been detected in human hepatoma cell lines and in human hepatocellular carcinoma (HCC); however, the contribution of COX-2 to the development of HCC remains controversial. COX-2 expression is higher in the non-tumoral tissue and inversely correlates with the differentiation grade of the tumor. COX-2 expression depends on the interplay between different cellular pathways involving both transcriptional and post-transcriptional regulation. The aim of this work was to assess whether COX-2 could be regulated by microRNAs in human hepatoma cell lines and in human HCC specimens since these molecules contribute to the regulation of genes implicated in cell growth and differentiation. Our results show that miR-16 silences COX-2 expression in hepatoma cells by two mechanisms: a) by binding directly to the microRNA response element (MRE) in the COX-2 3'-UTR promoting translational suppression of COX-2 mRNA; b) by decreasing the levels of the RNA-binding protein Human Antigen R (HuR). Furthermore, ectopic expression of miR-16 inhibits cell proliferation, promotes cell apoptosis and suppresses the ability of hepatoma cells to develop tumors in nude mice, partially through targeting COX-2. Moreover a reduced miR-16 expression tends to correlate to high levels of COX-2 protein in liver from patients affected by HCC. Our data show an important role for miR-16 as a post-transcriptional regulator of COX-2 in HCC and suggest the potential therapeutic application of miR-16 in those HCC with a high COX-2 expression.Fil: Agra Andrieu, Noelia. Consejo Superior de Investigaciones Cientificas; EspañaFil: Motiño, Omar. Consejo Superior de Investigaciones Cientificas; EspañaFil: Mayoral, Rafael. Consejo Superior de Investigaciones Cientificas; EspañaFil: Llorente Izquierdo, Cristina. Consejo Superior de Investigaciones Cientificas; EspañaFil: Fernández Alvarez, Ana Julia. Consejo Superior de Investigaciones Cientificas; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Boscá, Lisardo. Consejo Superior de Investigaciones Cientificas; EspañaFil: Casado, Marta. Consejo Superior de Investigaciones Cientificas; EspañaFil: Martin Sanz, Paloma. Consejo Superior de Investigaciones Cientificas; EspañaPublic Library Of Science2012-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/20865Agra Andrieu, Noelia; Motiño, Omar; Mayoral, Rafael; Llorente Izquierdo, Cristina; Fernández Alvarez, Ana Julia; et al.; Cyclooxygenase-2 is a target of microRNA-16 in human hepatoma cells; Public Library Of Science; Plos One; 7; 11; 11-2012; 1-151932-62031932-6203CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article/authors?id=10.1371/journal.pone.0050935info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0050935info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:26:46Zoai:ri.conicet.gov.ar:11336/20865instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:26:46.979CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Cyclooxygenase-2 is a target of microRNA-16 in human hepatoma cells
title Cyclooxygenase-2 is a target of microRNA-16 in human hepatoma cells
spellingShingle Cyclooxygenase-2 is a target of microRNA-16 in human hepatoma cells
Agra Andrieu, Noelia
Cycloxigenase
Epigenetics
miRNA
Cancer
title_short Cyclooxygenase-2 is a target of microRNA-16 in human hepatoma cells
title_full Cyclooxygenase-2 is a target of microRNA-16 in human hepatoma cells
title_fullStr Cyclooxygenase-2 is a target of microRNA-16 in human hepatoma cells
title_full_unstemmed Cyclooxygenase-2 is a target of microRNA-16 in human hepatoma cells
title_sort Cyclooxygenase-2 is a target of microRNA-16 in human hepatoma cells
dc.creator.none.fl_str_mv Agra Andrieu, Noelia
Motiño, Omar
Mayoral, Rafael
Llorente Izquierdo, Cristina
Fernández Alvarez, Ana Julia
Boscá, Lisardo
Casado, Marta
Martin Sanz, Paloma
author Agra Andrieu, Noelia
author_facet Agra Andrieu, Noelia
Motiño, Omar
Mayoral, Rafael
Llorente Izquierdo, Cristina
Fernández Alvarez, Ana Julia
Boscá, Lisardo
Casado, Marta
Martin Sanz, Paloma
author_role author
author2 Motiño, Omar
Mayoral, Rafael
Llorente Izquierdo, Cristina
Fernández Alvarez, Ana Julia
Boscá, Lisardo
Casado, Marta
Martin Sanz, Paloma
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cycloxigenase
Epigenetics
miRNA
Cancer
topic Cycloxigenase
Epigenetics
miRNA
Cancer
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Cyclooxygenase-2 (COX-2) expression has been detected in human hepatoma cell lines and in human hepatocellular carcinoma (HCC); however, the contribution of COX-2 to the development of HCC remains controversial. COX-2 expression is higher in the non-tumoral tissue and inversely correlates with the differentiation grade of the tumor. COX-2 expression depends on the interplay between different cellular pathways involving both transcriptional and post-transcriptional regulation. The aim of this work was to assess whether COX-2 could be regulated by microRNAs in human hepatoma cell lines and in human HCC specimens since these molecules contribute to the regulation of genes implicated in cell growth and differentiation. Our results show that miR-16 silences COX-2 expression in hepatoma cells by two mechanisms: a) by binding directly to the microRNA response element (MRE) in the COX-2 3'-UTR promoting translational suppression of COX-2 mRNA; b) by decreasing the levels of the RNA-binding protein Human Antigen R (HuR). Furthermore, ectopic expression of miR-16 inhibits cell proliferation, promotes cell apoptosis and suppresses the ability of hepatoma cells to develop tumors in nude mice, partially through targeting COX-2. Moreover a reduced miR-16 expression tends to correlate to high levels of COX-2 protein in liver from patients affected by HCC. Our data show an important role for miR-16 as a post-transcriptional regulator of COX-2 in HCC and suggest the potential therapeutic application of miR-16 in those HCC with a high COX-2 expression.
Fil: Agra Andrieu, Noelia. Consejo Superior de Investigaciones Cientificas; España
Fil: Motiño, Omar. Consejo Superior de Investigaciones Cientificas; España
Fil: Mayoral, Rafael. Consejo Superior de Investigaciones Cientificas; España
Fil: Llorente Izquierdo, Cristina. Consejo Superior de Investigaciones Cientificas; España
Fil: Fernández Alvarez, Ana Julia. Consejo Superior de Investigaciones Cientificas; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Boscá, Lisardo. Consejo Superior de Investigaciones Cientificas; España
Fil: Casado, Marta. Consejo Superior de Investigaciones Cientificas; España
Fil: Martin Sanz, Paloma. Consejo Superior de Investigaciones Cientificas; España
description Cyclooxygenase-2 (COX-2) expression has been detected in human hepatoma cell lines and in human hepatocellular carcinoma (HCC); however, the contribution of COX-2 to the development of HCC remains controversial. COX-2 expression is higher in the non-tumoral tissue and inversely correlates with the differentiation grade of the tumor. COX-2 expression depends on the interplay between different cellular pathways involving both transcriptional and post-transcriptional regulation. The aim of this work was to assess whether COX-2 could be regulated by microRNAs in human hepatoma cell lines and in human HCC specimens since these molecules contribute to the regulation of genes implicated in cell growth and differentiation. Our results show that miR-16 silences COX-2 expression in hepatoma cells by two mechanisms: a) by binding directly to the microRNA response element (MRE) in the COX-2 3'-UTR promoting translational suppression of COX-2 mRNA; b) by decreasing the levels of the RNA-binding protein Human Antigen R (HuR). Furthermore, ectopic expression of miR-16 inhibits cell proliferation, promotes cell apoptosis and suppresses the ability of hepatoma cells to develop tumors in nude mice, partially through targeting COX-2. Moreover a reduced miR-16 expression tends to correlate to high levels of COX-2 protein in liver from patients affected by HCC. Our data show an important role for miR-16 as a post-transcriptional regulator of COX-2 in HCC and suggest the potential therapeutic application of miR-16 in those HCC with a high COX-2 expression.
publishDate 2012
dc.date.none.fl_str_mv 2012-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/20865
Agra Andrieu, Noelia; Motiño, Omar; Mayoral, Rafael; Llorente Izquierdo, Cristina; Fernández Alvarez, Ana Julia; et al.; Cyclooxygenase-2 is a target of microRNA-16 in human hepatoma cells; Public Library Of Science; Plos One; 7; 11; 11-2012; 1-15
1932-6203
1932-6203
CONICET Digital
CONICET
url http://hdl.handle.net/11336/20865
identifier_str_mv Agra Andrieu, Noelia; Motiño, Omar; Mayoral, Rafael; Llorente Izquierdo, Cristina; Fernández Alvarez, Ana Julia; et al.; Cyclooxygenase-2 is a target of microRNA-16 in human hepatoma cells; Public Library Of Science; Plos One; 7; 11; 11-2012; 1-15
1932-6203
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article/authors?id=10.1371/journal.pone.0050935
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0050935
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
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:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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