title: Featured Article: Modulation of fetal hemoglobin in hereditary persistence of fetal hemoglobin deletion type-2, compared to Sicilian δβ-thalassemia, by BCL11A and SOX6-targeting microRNAs.
abstract: Hereditary persistence of fetal hemoglobin deletion type-2 (HPFH-2) and Sicilian-δβ-thalassemia are conditions described as large deletions of the human β-like globin cluster, with absent β-globin chains and a compensatory variable increase in γ-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 γ-globin expression. In this report, a possible association among the overexpression of miRNAs and the expression of the γ-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-δβ-thalassemia, 2 for HPFH-2 and 3 for controls after 13 days of culture. Some of these miRNAs may participate in γ-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 δβ-thalassemia and the increased expression of γ-globin in these conditions.
authors: Hemocentro-UNICAMP - SP, Brazil, São Paulo 13083-878, Brazil.
authors: Thais A
authors: TA
authors: Fornari
authors: Hemocentro-UNICAMP - SP, Brazil, São Paulo 13083-878, Brazil.
authors: Carolina
authors: C
authors: Lanaro
authors: Hemocentro-UNICAMP - SP, Brazil, São Paulo 13083-878, Brazil.
authors: Dulcinéia M
authors: DM
authors: Albuquerque
authors: Hemocentro-UNICAMP - SP, Brazil, São Paulo 13083-878, Brazil.
authors: Regiane
authors: R
authors: Ferreira
authors: Hemocentro-UNICAMP - SP, Brazil, São Paulo 13083-878, Brazil.
authors: Fernando F
authors: FF
authors: Costa
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D005319:Fetal Hemoglobin / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins; D055755:SOXD Transcription Factors / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000235:genetics*; D055538:delta-Thalassemia / Q000235:genetics*; D055545:gamma-Globins / Q000235:genetics* / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; C486563:BCL11A protein, human; D002352:Carrier Proteins; D035683:MicroRNAs; D009687:Nuclear Proteins; D012097:Repressor Proteins; C486270:SOX6 protein, human; D055755:SOXD Transcription Factors; D055544:beta-Globins; D055545:gamma-Globins; D005319:Fetal Hemoglobin
keywords: BCL11A; Hereditary persistence of fetal hemoglobin deletion type-2; SOX6; Sicilian-δβ-thalassemia; hemoglobinopathies; microRNAs