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BCL11A mRNA Targeting by miR-210: A Possible Network Regulating γ-Globin Gene Expression.

Abstract：

:The 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.

journal_name

Int J Mol Sci

journal_title

International journal of molecular sciences

authors

Gasparello J,Fabbri E,Bianchi N,Breveglieri G,Zuccato C,Borgatti M,Gambari R,Finotti A

doi

10.3390/ijms18122530

subject

Has Abstract

pub_date

2017-11-26 00:00:00

issue

12

issn

1422-0067

pii

ijms18122530

journal_volume

18

pub_type

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