Ferritin Heavy Subunit Silencing Blocks the Erythroid Commitment of K562 Cells via miR-150 up-Regulation and GATA-1 Repression
AbstractErythroid 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. View Full-Text
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Zolea, F.; Battaglia, A.M.; Chiarella, E.; Malanga, D.; Marco, C.D.; Bond, H.M.; Morrone, G.; Costanzo, F.; Biamonte, F. Ferritin Heavy Subunit Silencing Blocks the Erythroid Commitment of K562 Cells via miR-150 up-Regulation and GATA-1 Repression. Int. J. Mol. Sci. 2017, 18, 2167.
Zolea F, Battaglia AM, Chiarella E, Malanga D, Marco CD, Bond HM, Morrone G, Costanzo F, Biamonte F. Ferritin Heavy Subunit Silencing Blocks the Erythroid Commitment of K562 Cells via miR-150 up-Regulation and GATA-1 Repression. International Journal of Molecular Sciences. 2017; 18(10):2167.Chicago/Turabian Style
Zolea, Fabiana; Battaglia, Anna Martina; Chiarella, Emanuela; Malanga, Donatella; Marco, Carmela De; Bond, Heather Mandy; Morrone, Giovanni; Costanzo, Francesco; Biamonte, Flavia. 2017. "Ferritin Heavy Subunit Silencing Blocks the Erythroid Commitment of K562 Cells via miR-150 up-Regulation and GATA-1 Repression." Int. J. Mol. Sci. 18, no. 10: 2167.
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