BCL11A mRNA Targeting by miR-210: A Possible Network Regulating γ-Globin Gene Expression
AbstractThe involvement of microRNAs in the control of repressors of human γ-globin gene transcription has been firmly demonstrated, as described for the miR-486-3p mediated down-regulation of BCL11A. On the other hand, we have reported that miR-210 is involved in erythroid differentiation and, possibly, in γ-globin gene up-regulation. In the present study, we have identified the coding sequence of BCL11A as a possible target of miR-210. The following results sustain this hypothesis: (a) interactions between miR-210 and the miR-210 BCL11A site were demonstrated by SPR-based biomolecular interaction analysis (BIA); (b) the miR-210 site of BCL11A is conserved through molecular evolution; (c) forced expression of miR-210 leads to decrease of BCL11A-XL and increase of γ-globin mRNA content in erythroid cells, including erythroid precursors isolated from β-thalassemia patients. Our study suggests that the coding mRNA sequence of BCL11A can be targeted by miR-210. In addition to the theoretical point of view, these data are of interest from the applied point of view, supporting a novel strategy to inhibit BCL11A by mimicking miR-210 functions, accordingly with the concept supported by several papers and patent applications that inhibition of BCL11A is an efficient strategy for fetal hemoglobin induction in the treatment of β-thalassemia. View Full-Text
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Gasparello, J.; Fabbri, E.; Bianchi, N.; Breveglieri, G.; Zuccato, C.; Borgatti, M.; Gambari, R.; Finotti, A. BCL11A mRNA Targeting by miR-210: A Possible Network Regulating γ-Globin Gene Expression. Int. J. Mol. Sci. 2017, 18, 2530.
Gasparello J, Fabbri E, Bianchi N, Breveglieri G, Zuccato C, Borgatti M, Gambari R, Finotti A. BCL11A mRNA Targeting by miR-210: A Possible Network Regulating γ-Globin Gene Expression. International Journal of Molecular Sciences. 2017; 18(12):2530.Chicago/Turabian Style
Gasparello, Jessica; Fabbri, Enrica; Bianchi, Nicoletta; Breveglieri, Giulia; Zuccato, Cristina; Borgatti, Monica; Gambari, Roberto; Finotti, Alessia. 2017. "BCL11A mRNA Targeting by miR-210: A Possible Network Regulating γ-Globin Gene Expression." Int. J. Mol. Sci. 18, no. 12: 2530.
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