Regulation of ABO blood group antigen expression by miR ‐331‐3p and miR‐1908‐5p during hematopoietic stem cell differentiation

miRNAs were identified as important regulators of ABH antigen expression. miR ‐331‐3p and miR‐1908‐5p directly target glycosyltransferase A and B mRNA. The simultaneous targeting of the TF SP1 by miR‐331‐3p further enhances this effect, rendering SP1 incapable of binding to the ABO gene promoter, resulting in downregulation of blood group A antigen expression. AbstractThe ABO blood group system is the most important factor in clinical transfusion medicine and is implicated in a number of human diseases. ABO antigens are not confined to red blood cells (RBCs) and are widely expressed in a variety of human cells and tissues. To date, many alleles with variant ABO expression have been identified and in many cases trace to one of the>250 reported genetic variations in the respective glycosyltransferase. The role of microRNAs (miRNAs) in the regulation of blood group antigens during erythropoiesis has not been addressed, however. Here, we show that miR ‐331‐3p and miR‐1908‐5p directly target the mRNA of glycosyltransferases A and B. Expression levels of miR‐331‐3p and miR‐1908‐5p inversely correlated with levels of blood group A antigen. In addition, we found that overexpression of these miRNAs in hematopoietic stem cells led to a significantly reduced number of blood group A antigens per RBC. Simultaneous targeting of the transcription factor (TF) SP1 by miR‐331‐3p further enhanced these effects. The targeting rendered SP1 incapable of binding t...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Translational And Clinical Research Source Type: research