Cargando…

MicroRNA-146a and AMD3100, two ways to control CXCR4 expression in acute myeloid leukemias

CXCR4 is a negative prognostic marker in acute myeloid leukemias (AMLs). Therefore, it is necessary to develop novel ways to inhibit CXCR4 expression in leukemia. AMD3100 is an inhibitor of CXCR4 currently used to mobilize cancer cells. CXCR4 is a target of microRNA (miR)-146a that may represent a n...

Descripción completa

Detalles Bibliográficos
Autores principales: Spinello, I, Quaranta, M T, Riccioni, R, Riti, V, Pasquini, L, Boe, A, Pelosi, E, Vitale, A, Foà, R, Testa, U, Labbaye, C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3255264/
https://www.ncbi.nlm.nih.gov/pubmed/22829170
http://dx.doi.org/10.1038/bcj.2011.24
_version_ 1782220971102437376
author Spinello, I
Quaranta, M T
Riccioni, R
Riti, V
Pasquini, L
Boe, A
Pelosi, E
Vitale, A
Foà, R
Testa, U
Labbaye, C
author_facet Spinello, I
Quaranta, M T
Riccioni, R
Riti, V
Pasquini, L
Boe, A
Pelosi, E
Vitale, A
Foà, R
Testa, U
Labbaye, C
author_sort Spinello, I
collection PubMed
description CXCR4 is a negative prognostic marker in acute myeloid leukemias (AMLs). Therefore, it is necessary to develop novel ways to inhibit CXCR4 expression in leukemia. AMD3100 is an inhibitor of CXCR4 currently used to mobilize cancer cells. CXCR4 is a target of microRNA (miR)-146a that may represent a new tool to inhibit CXCR4 expression. We then investigated CXCR4 regulation by miR-146a in primary AMLs and found an inverse correlation between miR-146a and CXCR4 protein expression levels in all AML subtypes. As the lowest miR-146a expression levels were observed in M5 AML, we analyzed the control of CXCR4 expression by miR-146a in normal and leukemic monocytic cells and showed that the regulatory miR-146a/CXCR4 pathway operates during monocytopoiesis, but is deregulated in AMLs. AMD3100 treatment and miR-146a overexpression were used to inhibit CXCR4 in leukemic cells. AMD3100 treatment induces the decrease of CXCR4 protein expression, associated with miR-146a increase, and increases sensitivity of leukemic blast cells to cytotoxic drugs, this effect being further enhanced by miR-146a overexpression. Altogether our data indicate that miR-146a and AMD3100, acting through different mechanism, downmodulate CXCR4 protein levels, impair leukemic cell proliferation and then may be used in combination with anti-leukemia drugs, for development of new therapeutic strategies.
format Online
Article
Text
id pubmed-3255264
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-32552642012-01-11 MicroRNA-146a and AMD3100, two ways to control CXCR4 expression in acute myeloid leukemias Spinello, I Quaranta, M T Riccioni, R Riti, V Pasquini, L Boe, A Pelosi, E Vitale, A Foà, R Testa, U Labbaye, C Blood Cancer J Original Article CXCR4 is a negative prognostic marker in acute myeloid leukemias (AMLs). Therefore, it is necessary to develop novel ways to inhibit CXCR4 expression in leukemia. AMD3100 is an inhibitor of CXCR4 currently used to mobilize cancer cells. CXCR4 is a target of microRNA (miR)-146a that may represent a new tool to inhibit CXCR4 expression. We then investigated CXCR4 regulation by miR-146a in primary AMLs and found an inverse correlation between miR-146a and CXCR4 protein expression levels in all AML subtypes. As the lowest miR-146a expression levels were observed in M5 AML, we analyzed the control of CXCR4 expression by miR-146a in normal and leukemic monocytic cells and showed that the regulatory miR-146a/CXCR4 pathway operates during monocytopoiesis, but is deregulated in AMLs. AMD3100 treatment and miR-146a overexpression were used to inhibit CXCR4 in leukemic cells. AMD3100 treatment induces the decrease of CXCR4 protein expression, associated with miR-146a increase, and increases sensitivity of leukemic blast cells to cytotoxic drugs, this effect being further enhanced by miR-146a overexpression. Altogether our data indicate that miR-146a and AMD3100, acting through different mechanism, downmodulate CXCR4 protein levels, impair leukemic cell proliferation and then may be used in combination with anti-leukemia drugs, for development of new therapeutic strategies. Nature Publishing Group 2011-06 2011-06-24 /pmc/articles/PMC3255264/ /pubmed/22829170 http://dx.doi.org/10.1038/bcj.2011.24 Text en Copyright © 2011 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Original Article
Spinello, I
Quaranta, M T
Riccioni, R
Riti, V
Pasquini, L
Boe, A
Pelosi, E
Vitale, A
Foà, R
Testa, U
Labbaye, C
MicroRNA-146a and AMD3100, two ways to control CXCR4 expression in acute myeloid leukemias
title MicroRNA-146a and AMD3100, two ways to control CXCR4 expression in acute myeloid leukemias
title_full MicroRNA-146a and AMD3100, two ways to control CXCR4 expression in acute myeloid leukemias
title_fullStr MicroRNA-146a and AMD3100, two ways to control CXCR4 expression in acute myeloid leukemias
title_full_unstemmed MicroRNA-146a and AMD3100, two ways to control CXCR4 expression in acute myeloid leukemias
title_short MicroRNA-146a and AMD3100, two ways to control CXCR4 expression in acute myeloid leukemias
title_sort microrna-146a and amd3100, two ways to control cxcr4 expression in acute myeloid leukemias
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3255264/
https://www.ncbi.nlm.nih.gov/pubmed/22829170
http://dx.doi.org/10.1038/bcj.2011.24
work_keys_str_mv AT spinelloi microrna146aandamd3100twowaystocontrolcxcr4expressioninacutemyeloidleukemias
AT quarantamt microrna146aandamd3100twowaystocontrolcxcr4expressioninacutemyeloidleukemias
AT riccionir microrna146aandamd3100twowaystocontrolcxcr4expressioninacutemyeloidleukemias
AT ritiv microrna146aandamd3100twowaystocontrolcxcr4expressioninacutemyeloidleukemias
AT pasquinil microrna146aandamd3100twowaystocontrolcxcr4expressioninacutemyeloidleukemias
AT boea microrna146aandamd3100twowaystocontrolcxcr4expressioninacutemyeloidleukemias
AT pelosie microrna146aandamd3100twowaystocontrolcxcr4expressioninacutemyeloidleukemias
AT vitalea microrna146aandamd3100twowaystocontrolcxcr4expressioninacutemyeloidleukemias
AT foar microrna146aandamd3100twowaystocontrolcxcr4expressioninacutemyeloidleukemias
AT testau microrna146aandamd3100twowaystocontrolcxcr4expressioninacutemyeloidleukemias
AT labbayec microrna146aandamd3100twowaystocontrolcxcr4expressioninacutemyeloidleukemias