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

Autor(es)

Fornari, Thais A. ; Lanaro, Carolina ; Albuquerque, Dulcineia M. ; Ferreira, Regiane ; Costa, Fernando F.

• Tipo de documento: Artigo Científico
• Fonte: Experimental Biology and Medicine; v. 242, n. 3, p. 267-274, FEB 2017.
• Citações Web of Science: 1

Resumo

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)

• Processo FAPESP: 13/06679-5 - Avaliação do perfil de expressão de microRNAs em reticulócitos e em cultura de células CD34+ de indivíduos com PHHF-2 e de pacientes com Delta-beta-talassemia Siciliana
• Beneficiário: Thais Arouca Fornari Tavares
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado