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Ferritin Heavy Subunit Silencing Blocks the Erythroid Commitment of K562 Cells via miR-150 up-Regulation and GATA-1 Repression

Erythroid differentiation is a complex and multistep process during which an adequate supply of iron for hemoglobinization is required. The role of ferritin heavy subunit, in this process, has been mainly attributed to its capacity to maintain iron in a non-toxic form. We propose a new role for ferr...

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Autores principales: Zolea, Fabiana, Battaglia, Anna Martina, Chiarella, Emanuela, Malanga, Donatella, De Marco, Carmela, Bond, Heather Mandy, Morrone, Giovanni, Costanzo, Francesco, Biamonte, Flavia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666848/
https://www.ncbi.nlm.nih.gov/pubmed/29039805
http://dx.doi.org/10.3390/ijms18102167
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author Zolea, Fabiana
Battaglia, Anna Martina
Chiarella, Emanuela
Malanga, Donatella
De Marco, Carmela
Bond, Heather Mandy
Morrone, Giovanni
Costanzo, Francesco
Biamonte, Flavia
author_facet Zolea, Fabiana
Battaglia, Anna Martina
Chiarella, Emanuela
Malanga, Donatella
De Marco, Carmela
Bond, Heather Mandy
Morrone, Giovanni
Costanzo, Francesco
Biamonte, Flavia
author_sort Zolea, Fabiana
collection PubMed
description Erythroid differentiation is a complex and multistep process during which an adequate supply of iron for hemoglobinization is required. The role of ferritin heavy subunit, in this process, has been mainly attributed to its capacity to maintain iron in a non-toxic form. We propose a new role for ferritin heavy subunit (FHC) in controlling the erythroid commitment of K562 erythro-myeloid cells. FHC knockdown induces a change in the balance of GATA transcription factors and significantly reduces the expression of a repertoire of erythroid-specific genes, including α- and γ-globins, as well as CD71 and CD235a surface markers, in the absence of differentiation stimuli. These molecular changes are also reflected at the morphological level. Moreover, the ability of FHC-silenced K562 cells to respond to the erythroid-specific inducer hemin is almost completely abolished. Interestingly, we found that this new role for FHC is largely mediated via regulation of miR-150, one of the main microRNA implicated in the cell-fate choice of common erythroid/megakaryocytic progenitors. These findings shed further insight into the biological properties of FHCand delineate a role in erythroid differentiation where this protein does not act as a mere iron metabolism-related factor but also as a critical regulator of the expression of genes of central relevance for erythropoiesis.
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spelling pubmed-56668482017-11-09 Ferritin Heavy Subunit Silencing Blocks the Erythroid Commitment of K562 Cells via miR-150 up-Regulation and GATA-1 Repression Zolea, Fabiana Battaglia, Anna Martina Chiarella, Emanuela Malanga, Donatella De Marco, Carmela Bond, Heather Mandy Morrone, Giovanni Costanzo, Francesco Biamonte, Flavia Int J Mol Sci Article Erythroid differentiation is a complex and multistep process during which an adequate supply of iron for hemoglobinization is required. The role of ferritin heavy subunit, in this process, has been mainly attributed to its capacity to maintain iron in a non-toxic form. We propose a new role for ferritin heavy subunit (FHC) in controlling the erythroid commitment of K562 erythro-myeloid cells. FHC knockdown induces a change in the balance of GATA transcription factors and significantly reduces the expression of a repertoire of erythroid-specific genes, including α- and γ-globins, as well as CD71 and CD235a surface markers, in the absence of differentiation stimuli. These molecular changes are also reflected at the morphological level. Moreover, the ability of FHC-silenced K562 cells to respond to the erythroid-specific inducer hemin is almost completely abolished. Interestingly, we found that this new role for FHC is largely mediated via regulation of miR-150, one of the main microRNA implicated in the cell-fate choice of common erythroid/megakaryocytic progenitors. These findings shed further insight into the biological properties of FHCand delineate a role in erythroid differentiation where this protein does not act as a mere iron metabolism-related factor but also as a critical regulator of the expression of genes of central relevance for erythropoiesis. MDPI 2017-10-17 /pmc/articles/PMC5666848/ /pubmed/29039805 http://dx.doi.org/10.3390/ijms18102167 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zolea, Fabiana
Battaglia, Anna Martina
Chiarella, Emanuela
Malanga, Donatella
De Marco, Carmela
Bond, Heather Mandy
Morrone, Giovanni
Costanzo, Francesco
Biamonte, Flavia
Ferritin Heavy Subunit Silencing Blocks the Erythroid Commitment of K562 Cells via miR-150 up-Regulation and GATA-1 Repression
title Ferritin Heavy Subunit Silencing Blocks the Erythroid Commitment of K562 Cells via miR-150 up-Regulation and GATA-1 Repression
title_full Ferritin Heavy Subunit Silencing Blocks the Erythroid Commitment of K562 Cells via miR-150 up-Regulation and GATA-1 Repression
title_fullStr Ferritin Heavy Subunit Silencing Blocks the Erythroid Commitment of K562 Cells via miR-150 up-Regulation and GATA-1 Repression
title_full_unstemmed Ferritin Heavy Subunit Silencing Blocks the Erythroid Commitment of K562 Cells via miR-150 up-Regulation and GATA-1 Repression
title_short Ferritin Heavy Subunit Silencing Blocks the Erythroid Commitment of K562 Cells via miR-150 up-Regulation and GATA-1 Repression
title_sort ferritin heavy subunit silencing blocks the erythroid commitment of k562 cells via mir-150 up-regulation and gata-1 repression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666848/
https://www.ncbi.nlm.nih.gov/pubmed/29039805
http://dx.doi.org/10.3390/ijms18102167
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