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


Journal

Stem cells (Dayton, Ohio)
ISSN: 1549-4918
Titre abrégé: Stem Cells
Pays: England
ID NLM: 9304532

Informations de publication

Date de publication:
01 10 2020
Historique:
received: 07 01 2020
revised: 15 06 2020
accepted: 15 06 2020
pubmed: 6 7 2020
medline: 7 7 2021
entrez: 5 7 2020
Statut: ppublish

Résumé

The 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 traced 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 to the ABO gene promoter, causing further downregulation of blood group A antigen expression by up to 70%. Taken together, expression changes in these miRNAs may account for rare cases of weak A/B phenotypes that genetic variations in the glycosyltransferase coding region cannot explain. These results also suggest an explanation for the disappearance of ABH antigens during carcinogenesis and point to new therapeutic targets in ABO mismatched organ transplantation.

Identifiants

pubmed: 32621650
doi: 10.1002/stem.3251
doi:

Substances chimiques

Blood Group Antigens 0
MIRN1908 microRNA, human 0
MIRN331 microRNA, human 0
MicroRNAs 0
RNA, Messenger 0
Sp1 Transcription Factor 0
Glycosyltransferases EC 2.4.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1348-1362

Informations de copyright

©2020 The Authors. Stem Cells published by Wiley Periodicals LLC on behalf of AlphaMed Press.

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Auteurs

Romy Kronstein-Wiedemann (R)

Department of Experimental Transfusion Medicine, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Paulina Nowakowska (P)

German Red Cross Blood Donation Service North-East, Institute for Transfusion Medicine, Dresden, Germany.

Peter Milanov (P)

German Red Cross Blood Donation Service Baden-Württemberg/Hessen, Institute for Transfusion Medicine and Immunohematology, Clinics of the Johann Wolfgang Goethe University Frankfurt/M, Frankfurt/M, Germany.

Knut Gubbe (K)

German Red Cross Blood Donation Service North-East, Institute for Transfusion Medicine, Dresden, Germany.

Erhard Seifried (E)

German Red Cross Blood Donation Service Baden-Württemberg/Hessen, Institute for Transfusion Medicine and Immunohematology, Clinics of the Johann Wolfgang Goethe University Frankfurt/M, Frankfurt/M, Germany.

Peter Bugert (P)

German Red Cross Blood Donation Service Baden-Württemberg/Hessen, Institute for Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Triantafyllos Chavakis (T)

German Red Cross Blood Donation Service North-East, Institute for Transfusion Medicine, Dresden, Germany.
Institute for Clinical Chemistry and Laboratory Medicine, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Torsten Tonn (T)

Department of Experimental Transfusion Medicine, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
German Red Cross Blood Donation Service North-East, Institute for Transfusion Medicine, Dresden, Germany.

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