title: MicroRNA-23a mediates post-transcriptional regulation of CXCL12 in bone marrow stromal cells.
abstract: The chemokine CXCL12 regulates the interaction between hematopoietic stem and progenitor cells and bone marrow stromal cells. Although its relevance in the bone marrow niche is well recognized, the regulation of CXCL12 by microRNA is not completely understood. We transfected a library of 486 microRNA in the bone marrow stromal cell line SCP-1 and studied the expression of CXCL12. Twenty-seven microRNA were shown to downregulate expression of CXCL12. Eight microRNA (miR-23a, 130b, 135, 200b, 200c, 216, 222, and 602) interacted directly with the 3'UTR of CXCL12. Next, we determined that only miR-23a is predicted to bind to the 3'UTR and is strongly expressed in primary bone marrow stromal cells. Modulation of miR-23a changes the migratory potential of hematopoietic progenitor cells in co-culture experiments. We discovered that TGFB1 mediates its inhibitory effect on CXCL12 levels by upregulation of miR-23a. This process was partly reversed by miR-23a molecules. Finally, we determined an inverse expression of CXCL12 and miR-23a in stromal cells from patients with myelodys-plastic syndrome indicating that the interaction has a pathophysiological role. Here, we show for the first time that CXCL12-targeting miR23a regulates the functional properties of the hematopoietic niche.
authors.affiliation: Department of Medicine I, University Hospital Carl Gustav Carus, Dresden University of Technology, Germany Laleh.arabanian@gu.se.
authors.forename: Laleh S
authors.initials: LS
authors.lastname: Arabanian
authors.affiliation: Institute for Regenerative Cures, University of California, Davis, CA, USA.
authors.forename: Fernando A
authors.initials: FA
authors.lastname: Fierro
authors.affiliation: Department of Medicine I, University Hospital Carl Gustav Carus, Dresden University of Technology, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Stölzel
authors.affiliation: Department of Medicine I, University Hospital Carl Gustav Carus, Dresden University of Technology, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Heder
authors.affiliation: Medical Clinic of Internal Medicine and Cardiology, Dresden University of Technology, Germany.
authors.forename: David M
authors.initials: DM
authors.lastname: Poitz
authors.affiliation: Medical Clinic of Internal Medicine and Cardiology, Dresden University of Technology, Germany.
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Strasser
authors.affiliation: Department of Medicine I, University Hospital Carl Gustav Carus, Dresden University of Technology, Germany.
authors.forename: Manja
authors.initials: M
authors.lastname: Wobus
authors.affiliation: Department of Medicine I, University Hospital Carl Gustav Carus, Dresden University of Technology, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Borhäuser
authors.affiliation: Department of Medicine I, University Hospital Carl Gustav Carus, Dresden University of Technology, Germany.
authors.forename: Ruben A
authors.initials: RA
authors.lastname: Ferrer
authors.affiliation: Department of Medicine I, University Hospital Carl Gustav Carus, Dresden University of Technology, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Platzbecker
authors.affiliation: Experimental Surgery and Regenerative Medicine, Department of Surgery, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schieker
authors.affiliation: Experimental Surgery and Regenerative Medicine, Department of Surgery, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Denitsa
authors.initials: D
authors.lastname: Docheva
authors.affiliation: Department of Medicine I, University Hospital Carl Gustav Carus, Dresden University of Technology, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.affiliation: Department of Medicine I, University Hospital Carl Gustav Carus, Dresden University of Technology, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Illmer
mesh_terms: D002460:Cell Line; D054377:Chemokine CXCL12 / Q000235:genetics*; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D009190:Myelodysplastic Syndromes / Q000235:genetics; D034622:RNA Interference; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics; D015203:Reproducibility of Results; D014162:Transfection
chemical_list: D054377:Chemokine CXCL12; C552430:MIRN23a microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger