MicroRNA-23a mediates post-transcriptional regulation of CXCL12 in bone marrow stromal cells

Laleh S. Arabanian, Fernando A Fierro, Friedrich Stölzel, Carolin Heder, David M. Poitz, Ruth H. Strasser, Manja Wobus, Martin Borhäuser, Ruben A. Ferrer, Uwe Platzbecker, Matthias Schieker, Denitsa Docheva, Gerhard Ehninger, Thomas Illmer

Research output: Contribution to journalArticle

17 Scopus citations

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'fUTR 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 myelodysplastic 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.

Original languageEnglish (US)
Pages (from-to)997-1005
Number of pages9
JournalHaematologica
Volume99
Issue number6
DOIs
StatePublished - Jun 1 2014

ASJC Scopus subject areas

  • Hematology

Fingerprint Dive into the research topics of 'MicroRNA-23a mediates post-transcriptional regulation of CXCL12 in bone marrow stromal cells'. Together they form a unique fingerprint.

  • Cite this

    Arabanian, L. S., Fierro, F. A., Stölzel, F., Heder, C., Poitz, D. M., Strasser, R. H., Wobus, M., Borhäuser, M., Ferrer, R. A., Platzbecker, U., Schieker, M., Docheva, D., Ehninger, G., & Illmer, T. (2014). MicroRNA-23a mediates post-transcriptional regulation of CXCL12 in bone marrow stromal cells. Haematologica, 99(6), 997-1005. https://doi.org/10.3324/haematol.2013.097675