title: Modulation of microRNAs expression in hematopoietic stem cells treated with sodium butyrate in inducing fetal hemoglobin expression.
abstract: Context Inherited hemoglobin diseases are the most common single-gene disorders. Induction of fetal hemoglobin in beta hemoglobin disorders compensate for abnormal chain and ameliorate the clinical complications. Sodium butyrate is used conventionally for fetal hemoglobin induction; it can be replaced by safer therapeutic tools like microRNAs, small non-coding RNAs that control number of epigenetic mechanisms. Objective In this study, we compared the changes in the microRNAs of differentiated erythroid cells between control and sodium butyrate treated groups. The objective is to find significant association between these changes and gamma chain up regulation. Materials and methods First, CD133+hematopoietic stem cells were isolated from cord blood by magnetic cell sorting (MACS) technique. After proliferation, the cells were differentiated to erythroid lineage in culture medium by EPO, SCF, and IL3. Meanwhile, the test group was treated with sodium butyrate. Then, gamma chain upregulation was verified by qPCR technique. Finally, microRNA profiling was performed through microarray assay and some of them confirmed by qPCR. Result Results demonstrated that gamma chain was 5.9-fold upregulated in the treated group. Significant changes were observed at 76 microRNAs, in which 20 were up-regulated and 56 were down-regulated. Discussion Five of these microRNAs including U101, hsa-miR-4726-5p, hsa-miR7109 5p, hsa-miR3663, and hsa-miR940 had significant changes in expression and volume. Conclusion In conclusion, it can be assumed that sodium butyrate can up-regulate gamma chain gene, and change miRNAs expression. These results can be profitable in future studies to find therapeutic goal suitable for such disorders.
authors.affiliation: a Faculty of Medicine , Qaem Hospital, Mashhad University of Medical Sciences and Health Care Services , Mashhad , Iran.
authors.forename: Behnoosh
authors.initials: B
authors.lastname: Tayebi
authors.affiliation: a Faculty of Medicine , Qaem Hospital, Mashhad University of Medical Sciences and Health Care Services , Mashhad , Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Abrishami
authors.affiliation: b Hematology Department, School of Allied Medical , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Shaban
authors.initials: S
authors.lastname: Alizadeh
authors.affiliation: b Hematology Department, School of Allied Medical , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Neda
authors.initials: N
authors.lastname: Minayi
authors.affiliation: c Amol Faculty of Paramedical Sciences , Mazandaran University of Medical Sciences , Sari , Iran.|d Hematology and Oncology Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Mozhdeh
authors.initials: M
authors.lastname: Mohammadian
authors.affiliation: e Department of Hematology, Faculty of Medical Sciences , Tarbiat Modares University , Tehran , Iran.
authors.forename: Masoud
authors.initials: M
authors.lastname: Soleimani
authors.affiliation: f Taleghani Bone Marrow Transplantation Center, Shahid Beheshti University of Medical Sciences , Tehran , Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Dehghanifard
authors.affiliation: g Immunology Department , Iran University of Medical Science , Tehran , Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Atwan
authors.affiliation: a Faculty of Medicine , Qaem Hospital, Mashhad University of Medical Sciences and Health Care Services , Mashhad , Iran.
authors.forename: Monireh
authors.initials: M
authors.lastname: Ajami
authors.affiliation: e Department of Hematology, Faculty of Medical Sciences , Tarbiat Modares University , Tehran , Iran.
authors.forename: Mansoureh
authors.initials: M
authors.lastname: Ajami
mesh_terms: D020148:Butyric Acid / Q000494:pharmacology*; D002478:Cells, Cultured; D005319:Fetal Hemoglobin / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D035683:MicroRNAs; D020148:Butyric Acid; D005319:Fetal Hemoglobin
keywords: Fetal hemoglobin; hematopoietic stem cell; microRNA; microarray; sickle cell anemia; sodium butyrate; thalassemia