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Peptide nucleic acids targeting β-globin mRNAs selectively inhibit hemoglobin production in murine erythroleukemia cells

In the treatment of hemoglobinopathies, amending altered hemoglobins and/or globins produced in excess is an important part of therapeutic strategies and the selective inhibition of globin production may be clinically beneficial. Therefore the development of drug-based methods for the selective inhi...

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Autores principales: MONTAGNER, GIULIA, GEMMO, CHIARA, FABBRI, ENRICA, MANICARDI, ALEX, ACCARDO, IGEA, BIANCHI, NICOLETTA, FINOTTI, ALESSIA, BREVEGLIERI, GIULIA, SALVATORI, FRANCESCA, BORGATTI, MONICA, LAMPRONTI, ILARIA, BRESCIANI, ALBERTO, ALTAMURA, SERGIO, CORRADINI, ROBERTO, GAMBARI, ROBERTO
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249754/
https://www.ncbi.nlm.nih.gov/pubmed/25405921
http://dx.doi.org/10.3892/ijmm.2014.2005
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author MONTAGNER, GIULIA
GEMMO, CHIARA
FABBRI, ENRICA
MANICARDI, ALEX
ACCARDO, IGEA
BIANCHI, NICOLETTA
FINOTTI, ALESSIA
BREVEGLIERI, GIULIA
SALVATORI, FRANCESCA
BORGATTI, MONICA
LAMPRONTI, ILARIA
BRESCIANI, ALBERTO
ALTAMURA, SERGIO
CORRADINI, ROBERTO
GAMBARI, ROBERTO
author_facet MONTAGNER, GIULIA
GEMMO, CHIARA
FABBRI, ENRICA
MANICARDI, ALEX
ACCARDO, IGEA
BIANCHI, NICOLETTA
FINOTTI, ALESSIA
BREVEGLIERI, GIULIA
SALVATORI, FRANCESCA
BORGATTI, MONICA
LAMPRONTI, ILARIA
BRESCIANI, ALBERTO
ALTAMURA, SERGIO
CORRADINI, ROBERTO
GAMBARI, ROBERTO
author_sort MONTAGNER, GIULIA
collection PubMed
description In the treatment of hemoglobinopathies, amending altered hemoglobins and/or globins produced in excess is an important part of therapeutic strategies and the selective inhibition of globin production may be clinically beneficial. Therefore the development of drug-based methods for the selective inhibition of globin accumulation is required. In this study, we employed peptide nucleic acids (PNAs) to alter globin gene expression. The main conclusion of the present study was that PNAs designed to target adult murine β-globin mRNA inhibit hemoglobin accumulation and erythroid differentiation of murine erythroleukemia (MEL) cells with high efficiency and fair selectivity. No major effects were observed on cell proliferation. Our study supports the concept that PNAs may be used to target mRNAs that, similar to globin mRNAs, are expressed at very high levels in differentiating erythroid cells. Our data suggest that PNAs inhibit the excess production of globins involved in the pathophysiology of hemoglobinopathies.
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spelling pubmed-42497542014-12-02 Peptide nucleic acids targeting β-globin mRNAs selectively inhibit hemoglobin production in murine erythroleukemia cells MONTAGNER, GIULIA GEMMO, CHIARA FABBRI, ENRICA MANICARDI, ALEX ACCARDO, IGEA BIANCHI, NICOLETTA FINOTTI, ALESSIA BREVEGLIERI, GIULIA SALVATORI, FRANCESCA BORGATTI, MONICA LAMPRONTI, ILARIA BRESCIANI, ALBERTO ALTAMURA, SERGIO CORRADINI, ROBERTO GAMBARI, ROBERTO Int J Mol Med Articles In the treatment of hemoglobinopathies, amending altered hemoglobins and/or globins produced in excess is an important part of therapeutic strategies and the selective inhibition of globin production may be clinically beneficial. Therefore the development of drug-based methods for the selective inhibition of globin accumulation is required. In this study, we employed peptide nucleic acids (PNAs) to alter globin gene expression. The main conclusion of the present study was that PNAs designed to target adult murine β-globin mRNA inhibit hemoglobin accumulation and erythroid differentiation of murine erythroleukemia (MEL) cells with high efficiency and fair selectivity. No major effects were observed on cell proliferation. Our study supports the concept that PNAs may be used to target mRNAs that, similar to globin mRNAs, are expressed at very high levels in differentiating erythroid cells. Our data suggest that PNAs inhibit the excess production of globins involved in the pathophysiology of hemoglobinopathies. D.A. Spandidos 2015-01 2014-11-14 /pmc/articles/PMC4249754/ /pubmed/25405921 http://dx.doi.org/10.3892/ijmm.2014.2005 Text en Copyright © 2015, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Articles
MONTAGNER, GIULIA
GEMMO, CHIARA
FABBRI, ENRICA
MANICARDI, ALEX
ACCARDO, IGEA
BIANCHI, NICOLETTA
FINOTTI, ALESSIA
BREVEGLIERI, GIULIA
SALVATORI, FRANCESCA
BORGATTI, MONICA
LAMPRONTI, ILARIA
BRESCIANI, ALBERTO
ALTAMURA, SERGIO
CORRADINI, ROBERTO
GAMBARI, ROBERTO
Peptide nucleic acids targeting β-globin mRNAs selectively inhibit hemoglobin production in murine erythroleukemia cells
title Peptide nucleic acids targeting β-globin mRNAs selectively inhibit hemoglobin production in murine erythroleukemia cells
title_full Peptide nucleic acids targeting β-globin mRNAs selectively inhibit hemoglobin production in murine erythroleukemia cells
title_fullStr Peptide nucleic acids targeting β-globin mRNAs selectively inhibit hemoglobin production in murine erythroleukemia cells
title_full_unstemmed Peptide nucleic acids targeting β-globin mRNAs selectively inhibit hemoglobin production in murine erythroleukemia cells
title_short Peptide nucleic acids targeting β-globin mRNAs selectively inhibit hemoglobin production in murine erythroleukemia cells
title_sort peptide nucleic acids targeting β-globin mrnas selectively inhibit hemoglobin production in murine erythroleukemia cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249754/
https://www.ncbi.nlm.nih.gov/pubmed/25405921
http://dx.doi.org/10.3892/ijmm.2014.2005
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