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

ABSTRACT: The involvement of microRNAs in the control of repressors of human ?-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 ?-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 ?-globin mRNA content in erythroid cells, including erythroid precursors isolated from ?-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 ?-thalassemia.

SUBMITTER: Gasparello J 

PROVIDER: S-EPMC5751133 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature