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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Modulation of fetal hemoglobin in hereditary persistence of fetal hemoglobin deletion type-2, compared to Sicilian delta beta-thalassemia, by BCL11A and SOX6-targeting microRNAs

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Author(s):
Fornari, Thais A. ; Lanaro, Carolina ; Albuquerque, Dulcineia M. ; Ferreira, Regiane ; Costa, Fernando F.
Total Authors: 5
Document type: Journal article
Source: Experimental Biology and Medicine; v. 242, n. 3, p. 267-274, FEB 2017.
Web of Science Citations: 1
Abstract

Hereditary persistence of fetal hemoglobin deletion type-2 (HPFH-2) and Sicilian-delta beta-thalassemia are conditions described as large deletions of the human beta-like globin cluster, with absent beta-globin chains and a compensatory variable increase in gamma-globin. HPFH, in general, may be distinguished from DB-Thalassemia by higher fetal hemoglobin (HbF) levels, absence of anemia and hypochromic and microcytic erythrocytes. MicroRNAs (miRNAs) regulate a range of cellular processes including erythropoiesis and regulation of transcription factors such as the BCL11A and SOX6 genes, which are related to the regulation of gamma-globin expression. In this report, a possible association among the overexpression of miRNAs and the expression of the gamma-globin gene was analyzed in these two conditions. Forty-nine differentially expressed miRNAs were identified by microarrays in CD34+-derived erythroid cells of two subjects heterozygous for Sicilian-delta beta-thalassemia, 2 for HPFH-2 and 3 for controls after 13 days of culture. Some of these miRNAs may participate in gamma-globin gene regulation and red blood cell function. The BCL11A gene was found to be potentially targeted by 12 miRNAs that were up-regulated in HPFH-2 or in DB-Thal. A down-regulation of BCL11A gene expression in HPFH-2 was verified by quantitative polymerase chain reaction. These data suggest an important action for miRNA that may partially explain the phenotypic differences between HPFH-2 and Sicilian delta beta-thalassemia and the increased expression of gamma-globin in these conditions. (AU)

FAPESP's process: 13/06679-5 - Evaluation of the expression profile of microRNAs in reticulocytes and in CD34(+)-derived erythroid cells from individuals with HPFH-2 and patients with Sicilian Delta-beta-thalassemia
Grantee:Thais Arouca Fornari Tavares
Support Opportunities: Scholarships in Brazil - Post-Doctoral