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

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 d...

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Autores principales: Noelia Agra Andrieu, Omar Motiño, Rafael Mayoral, Cristina Llorente Izquierdo, Ana Fernández-Alvarez, Lisardo Boscá, Marta Casado, Paloma Martín-Sanz
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Publicado: Public Library of Science (PLoS) 2012
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Acceso en línea:https://doaj.org/article/e19f93e6afc54af6a5910cebb21ed688
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spelling oai:doaj.org-article:e19f93e6afc54af6a5910cebb21ed6882021-11-18T08:06:38ZCyclooxygenase-2 is a target of microRNA-16 in human hepatoma cells.1932-620310.1371/journal.pone.0050935https://doaj.org/article/e19f93e6afc54af6a5910cebb21ed6882012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23226427/?tool=EBIhttps://doaj.org/toc/1932-6203Cyclooxygenase-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.Noelia Agra AndrieuOmar MotiñoRafael MayoralCristina Llorente IzquierdoAna Fernández-AlvarezLisardo BoscáMarta CasadoPaloma Martín-SanzPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e50935 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Noelia Agra Andrieu
Omar Motiño
Rafael Mayoral
Cristina Llorente Izquierdo
Ana Fernández-Alvarez
Lisardo Boscá
Marta Casado
Paloma Martín-Sanz
Cyclooxygenase-2 is a target of microRNA-16 in human hepatoma cells.
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.
format article
author Noelia Agra Andrieu
Omar Motiño
Rafael Mayoral
Cristina Llorente Izquierdo
Ana Fernández-Alvarez
Lisardo Boscá
Marta Casado
Paloma Martín-Sanz
author_facet Noelia Agra Andrieu
Omar Motiño
Rafael Mayoral
Cristina Llorente Izquierdo
Ana Fernández-Alvarez
Lisardo Boscá
Marta Casado
Paloma Martín-Sanz
author_sort Noelia Agra Andrieu
title Cyclooxygenase-2 is a target of microRNA-16 in human hepatoma cells.
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.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/e19f93e6afc54af6a5910cebb21ed688
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