BCL11A mRNA Targeting by miR-210: A Possible Network Regulating γ-Globin Gene Expression.
BCL11A mRNA Targeting by miR-210: A Possible Network Regulating γ-Globin Gene Expression.
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DOI：
10.3390/ijms18122530
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发表时间：
2017-11-26
影响因子：
5.6
通讯作者：
Finotti A
中科院分区：
文献类型：
--
作者：
Gasparello J;Fabbri E;Bianchi N;Breveglieri G;Zuccato C;Borgatti M;Gambari R;Finotti A
已经明确证明microRNA参与人γ-珠蛋白基因转录的阻遏物的控制，如关于miR-486 - 3p介导的BCL 11 A下调所述。另一方面，我们已经报道了miR-210参与红系分化，并且可能参与γ-珠蛋白基因的上调。在本研究中，我们已经确定了BCL 11A的编码序列作为miR-210的可能靶点。以下结果支持这一假设：（a）基于SPR的生物分子相互作用分析（BIA）证实了miR-210与miR-210 BCL 11 A位点之间的相互作用：（B）BCL 11 A的miR-210位点在分子进化中是保守的;（c）miR-210的强制表达导致红系细胞中BCL11A-XL的减少和γ-珠蛋白mRNA含量的增加，包括从β-地中海贫血患者分离的红系前体。我们的研究表明，BCL 11A的编码mRNA序列可以被miR-210靶向。除了理论观点之外，从应用观点来看，这些数据也是令人感兴趣的，支持通过模拟miR-210功能来抑制BCL 11A的新策略，因此具有由几篇论文和专利申请支持的概念，即抑制BCL 11A是治疗β-地中海贫血中胎儿血红蛋白诱导的有效策略。
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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影响因子：
2.6
作者：
Choong, Meng Ling;Yang, Henry He;McNiece, Ian
通讯作者：
McNiece, Ian
影响因子：
14.9
作者：
Griffiths-Jones, S
通讯作者：
Griffiths-Jones, S
影响因子：
4
作者：
Bianchi, Nicoletta;Cosenza, Lucia Carmela;Paciaroni, Katia
通讯作者：
Paciaroni, Katia
影响因子：
3.1
作者：
Fibach, Eitan;Bianchi, Nicoletta;Gambari, Roberto
通讯作者：
Gambari, Roberto
DOI：
10.3324/haematol.2008.002345
发表时间：
2009-04-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Felli, Nadia;Pedini, Francesca;Marziali, Giovanna
通讯作者：
Marziali, Giovanna