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.

MIR29B mediates epigenetic mechanisms of HBG gene activation

“…Several research efforts have focused on identifying miRNA genes that regulate HBG expression during haemoglobin switching (Gasparello et al , ; Hojjati et al , ; Lai et al , ; Sun et al , ; Obeidi et al , ; Saki et al , ; Tayebi et al , ; Guda et al , ; De Vasconcellos et al , ; Bianchi et al , ). Bianchi et al () identified the upregulation of MIR210 by microarray analysis of erythroid precursors from a thalassaemia patient with high HbF levels; they also demonstrated that mithramycin targeted MIR210 as a mechanism of HBG activation in K562 cells (Bianchi et al , ).…”

Profiling and characterization of microRNAs responding to sodium butyrate treatment in A549 cells

“…To date, the roles of butyrate in regulating expression of encoded genes have been intensively investigated; however, there are few reports on noncoding RNAs, especially on microRNAs. In NaB treated hematopoietic stem cells, 76 microRNAs were significantly induced such as hsa‐miR‐4726‐5p, hsa‐miR7109‐5p, hsa‐miR3663, and hsa‐miR940 screened by microarray . In HCT‐116 cells, microarray was also used to detect the microRNAs response to butyrate treatment, 44 miRNAs were found to be significantly changed in expression .…”

Sickle Cell Anaemia- A Synopsis of the Inherited Ailment

“…It is suggested that sodium butyrate treatment can be replaced by safer therapeutic tools like microRNAs, small non-coding RNAs that control number of epigenetic mechanisms. In a study by Tayabi and colleagues, it was demonstrated that gamma chain was 5.9-fold up-regulated in the treated group [84].…”

“…Instead of leaving the cell to make its own error-prone repairs to the CRISPR-induced cuts, researchers supply further guidance by delivering a strand of DNA that contains the corrected snippet of the haemoglobin sequence-a kind of 'repeat after me'. This approach is called homologydirected repair [84].…”