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.
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Authors | Jessica Gasparello, Enrica Fabbri, Nicoletta Bianchi, Giulia Breveglieri, Cristina Zuccato, Monica Borgatti, Roberto Gambari, Alessia Finotti |
Journal | International journal of molecular sciences
(Int J Mol Sci)
Vol. 18
Issue 12
(Nov 26 2017)
ISSN: 1422-0067 [Electronic] Switzerland |
PMID | 29186860
(Publication Type: Journal Article)
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Chemical References |
- BCL11A protein, human
- Carrier Proteins
- MIRN210 microRNA, human
- MicroRNAs
- Nuclear Proteins
- RNA, Messenger
- Repressor Proteins
- gamma-Globins
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Topics |
- Carrier Proteins
(genetics, metabolism)
- Cell Line, Tumor
- Erythroid Precursor Cells
(metabolism)
- Gene Regulatory Networks
- Humans
- MicroRNAs
(genetics, metabolism)
- Nuclear Proteins
(genetics, metabolism)
- RNA, Messenger
(genetics, metabolism)
- Repressor Proteins
- beta-Thalassemia
(genetics)
- gamma-Globins
(genetics, metabolism)
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