RUNX1 interacts with lncRNA SMANTIS to regulate monocytic cell functions
Monocytes, the circulating macrophage precursors, contribute to diseases like atherosclerosis and asthma. Long non-coding RNAs (lncRNAs) have been shown to modulate the phenotype and inflammatory capacity of monocytes. We previously discovered the lncRNA SMANTIS, which contributes to cellular phenotype expression by controlling BRG1 in mesenchymal cells. Here, we report that SMANTIS is particularly highly expressed in monocytes and lost during differentiation into macrophages. Moreover, different types of myeloid leukemia presented specific SMANTIS expression patterns. Interaction studies revealed that SMANTIS binds RUNX1, a transcription factor frequently mutated in AML, primarily through its Alu-element on the RUNT domain. RNA-seq after CRISPR/Cas9-mediated deletion of SMANTIS or RUNX1 revealed an association with cell adhesion and both limited the monocyte adhesion to endothelial cells. Mechanistically, SMANTIS KO reduced RUNX1 genomic binding and altered the interaction of RUNX1 with EP300 and CBFB. Collectively, SMANTIS interacts with RUNX1 and attenuates monocyte adhesion, which might limit monocyte vascular egress.
Authors
- Ilka Wittig (ORCID: https://orcid.org/0000-0002-9751-8054)
- Stefan Knapp (ORCID: https://orcid.org/0000-0001-5995-6494)
- Thomas Oellerich (ORCID: https://orcid.org/0000-0001-6570-6125)
- James A. Oo (ORCID: https://orcid.org/0000-0002-2934-7580)
- L. Weiss (ORCID: https://orcid.org/0009-0005-4574-8455)
- Tom Teichmann (ORCID: https://orcid.org/0009-0009-5402-3834)
- Andreas Weigert (ORCID: https://orcid.org/0000-0002-7529-1952)
- Michael A. Rieger (ORCID: https://orcid.org/0000-0002-4158-5872)
- Sebastian Wolf (ORCID: https://orcid.org/0000-0001-5298-8901)
- Timothy Warwick (ORCID: https://orcid.org/0000-0002-6804-2931)
- Simonida Zehr (ORCID: https://orcid.org/0009-0005-8510-657X)
- Rajkumar Savai (ORCID: https://orcid.org/0000-0003-1538-2091)
- Matthias S. Leisegang (ORCID: https://orcid.org/0000-0002-6084-6484)
- Stefan Günther (ORCID: https://orcid.org/0000-0002-5594-4549)
- Judit Izquierdo Ponce
- Ralf P. Brandes (ORCID: https://orcid.org/0000-0002-8035-0048)
- Tessa Schmachtel
- Katalin Pálfi
- Julia Stötzel (ORCID: https://orcid.org/0009-0008-7398-5847)
- Alicia Schneider
Institutions
- Goethe University Frankfurt (DE)
- Justus-Liebig-Universität Gießen (DE)
- Frankfurt Institute for Advanced Studies (DE)
- Max Planck Institute for Heart and Lung Research (DE)
- German Centre for Cardiovascular Research (DE)
- University Hospital Frankfurt (DE)
- Cardio-Pulmonary Institute (DE)
- Frankfurt Cancer Institute (DE)
- Deutsches Konsortium für Translationale Krebsforschung (DE)
Publication Details
- Journal
- Communications Biology
- Published
- 2024-09-13
- DOI
- https://doi.org/10.1038/s42003-024-06794-2
- Citations
- 4
- Primary Topic
- Cancer-related molecular mechanisms research
- Type
- article
- Field-Weighted Citation Impact
- 1.14
Funders
- Deutsches Zentrum für Herz-Kreislaufforschung
- Deutsche Forschungsgemeinschaft