The rescue of miR-148a expression in pancreatic cancer: an inappropriate therapeutic tool.

MicroRNAs are small non-coding RNAs that physiologically modulate proteins expression, and regulate numerous cellular mechanisms. Alteration of microRNA expression has been described in cancer and is associated to tumor initiation and progression. The microRNA 148a (miR-148a) is frequently down-regu...

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Autores principales: Yannick Delpu, Hubert Lulka, Flavie Sicard, Nathalie Saint-Laurent, Frédéric Lopez, Naïma Hanoun, Louis Buscail, Pierre Cordelier, Jérôme Torrisani
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/42695a09c3c249bf9e5d1226d06f4ee3
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spelling oai:doaj.org-article:42695a09c3c249bf9e5d1226d06f4ee32021-11-18T07:59:08ZThe rescue of miR-148a expression in pancreatic cancer: an inappropriate therapeutic tool.1932-620310.1371/journal.pone.0055513https://doaj.org/article/42695a09c3c249bf9e5d1226d06f4ee32013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23383211/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203MicroRNAs are small non-coding RNAs that physiologically modulate proteins expression, and regulate numerous cellular mechanisms. Alteration of microRNA expression has been described in cancer and is associated to tumor initiation and progression. The microRNA 148a (miR-148a) is frequently down-regulated in cancer. We previously demonstrated that its down-regulation by DNA hypermethylation is an early event in pancreatic ductal adenocarcinoma (PDAC) carcinogenesis, suggesting a tumor suppressive function. Here, we investigate the potential role of miR-148a over-expression in PDAC as a therapeutic tool. We first report the consequences of miR-148a over-expression in PDAC cell lines. We demonstrate that miR-148a over-expression has no dramatic effect on cell proliferation and cell chemo-sensitivity in four well described PDAC cell lines. We also investigate the modulation of protein expression by a global proteomic approach (2D-DIGE). We show that despite its massive over-expression, miR-148a weakly modulates protein expression, thus preventing the identification of protein targets in PDAC cell lines. More importantly, in vivo data demonstrate that modulating miR-148a expression either in the epithelia tumor cells and/or in the tumor microenvironment does not impede tumor growth. Taken together, we demonstrate herein that miR-148a does not impact PDAC proliferation both in vitro and in vivo thus suggesting a weak potential as a therapeutic tool.Yannick DelpuHubert LulkaFlavie SicardNathalie Saint-LaurentFrédéric LopezNaïma HanounLouis BuscailPierre CordelierJérôme TorrisaniPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e55513 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Yannick Delpu
Hubert Lulka
Flavie Sicard
Nathalie Saint-Laurent
Frédéric Lopez
Naïma Hanoun
Louis Buscail
Pierre Cordelier
Jérôme Torrisani
The rescue of miR-148a expression in pancreatic cancer: an inappropriate therapeutic tool.
description MicroRNAs are small non-coding RNAs that physiologically modulate proteins expression, and regulate numerous cellular mechanisms. Alteration of microRNA expression has been described in cancer and is associated to tumor initiation and progression. The microRNA 148a (miR-148a) is frequently down-regulated in cancer. We previously demonstrated that its down-regulation by DNA hypermethylation is an early event in pancreatic ductal adenocarcinoma (PDAC) carcinogenesis, suggesting a tumor suppressive function. Here, we investigate the potential role of miR-148a over-expression in PDAC as a therapeutic tool. We first report the consequences of miR-148a over-expression in PDAC cell lines. We demonstrate that miR-148a over-expression has no dramatic effect on cell proliferation and cell chemo-sensitivity in four well described PDAC cell lines. We also investigate the modulation of protein expression by a global proteomic approach (2D-DIGE). We show that despite its massive over-expression, miR-148a weakly modulates protein expression, thus preventing the identification of protein targets in PDAC cell lines. More importantly, in vivo data demonstrate that modulating miR-148a expression either in the epithelia tumor cells and/or in the tumor microenvironment does not impede tumor growth. Taken together, we demonstrate herein that miR-148a does not impact PDAC proliferation both in vitro and in vivo thus suggesting a weak potential as a therapeutic tool.
format article
author Yannick Delpu
Hubert Lulka
Flavie Sicard
Nathalie Saint-Laurent
Frédéric Lopez
Naïma Hanoun
Louis Buscail
Pierre Cordelier
Jérôme Torrisani
author_facet Yannick Delpu
Hubert Lulka
Flavie Sicard
Nathalie Saint-Laurent
Frédéric Lopez
Naïma Hanoun
Louis Buscail
Pierre Cordelier
Jérôme Torrisani
author_sort Yannick Delpu
title The rescue of miR-148a expression in pancreatic cancer: an inappropriate therapeutic tool.
title_short The rescue of miR-148a expression in pancreatic cancer: an inappropriate therapeutic tool.
title_full The rescue of miR-148a expression in pancreatic cancer: an inappropriate therapeutic tool.
title_fullStr The rescue of miR-148a expression in pancreatic cancer: an inappropriate therapeutic tool.
title_full_unstemmed The rescue of miR-148a expression in pancreatic cancer: an inappropriate therapeutic tool.
title_sort rescue of mir-148a expression in pancreatic cancer: an inappropriate therapeutic tool.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/42695a09c3c249bf9e5d1226d06f4ee3
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