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Long Noncoding RNA MANTIS Facilitates Endothelial Angiogenic Function.

Matthias S Leisegang1, Christian Fork1, Ivana Josipovic1

  • 1From Institute for Cardiovascular Physiology (M.S.L., C.F., I.J., M.J.M., J.E., F.M., R.P.B.), Functional Proteomics, SFB 815 Core Unit, Faculty of Medicine (F.M.R., J.H., I.W.), Institute of Vascular Signalling (J.H.), Institute of Cardiovascular Regeneration (P.H. Y.P., S.U., K.S., R.A.B., S.D.), Department of Neurosurgery (T.M.F.), Pharmazentrum Frankfurt, Institute of General Pharmacology and Toxicology (K.D.), Goethe University, Germany; ECCPS Bioinformatics and Sequencing Facility (J.P., S.G., C.K., M.L.) and Department of Lung Development and Remodeling (C.V., S.S.P.), Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany; Institute of Neurology (K.H.P., M.M., K.D.); Department of Vascular and Endovascular Surgery, Klinikum Rechts der Isar, Technical University Munich, Germany (L.M.); Luxembourg Centre of Neuropathology (M.M.); Laboratoire National de Santé, Dudelange, Luxembourg (M.M.); Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette (M.M.); NORLUX Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health (M.M.); Cardiovascular Innovation Institute, University of Louisville, KY (S.U.); Department of Internal Medicine, Member of the German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany (R.T.S., N.W., S.S.P.); Department of Medicine, Duke University and Durham VA Medical Center, NC (F.J.M.); and German Center of Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt, Germany (M.S.L., C.F., I.J., J.H., J.E., P.H., F.M., Y.P., K.H.P., K.S., I.W., R.A.B., S.D., R.P.B.).

Circulation
|March 30, 2017
PubMed
Summary
This summary is machine-generated.

This study identifies MANTIS, a novel long noncoding RNA (lncRNA), as crucial for endothelial cell function and angiogenesis. MANTIS regulates gene transcription by interacting with chromatin remodeling complexes.

Keywords:
RNA, long noncodingepigenomicsglioblastomahypertension, pulmonaryneovascularization, physiologic

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Endothelial cell angiogenic function is vital but incompletely understood.
  • The role of long noncoding RNAs (lncRNAs) in endothelial cell regulation is largely unexplored.

Purpose of the Study:

  • Identify novel, functionally significant endothelial lncRNAs.
  • Investigate the regulatory mechanisms and functional impact of identified lncRNAs.

Main Methods:

  • Exon-array analysis and JARID1B knockdown in human umbilical vein endothelial cells.
  • RNA pulldown, mass spectrometry, ChIP-seq, CRISPR-Cas9, and gene expression analysis.
  • Analysis of patient samples (lung, glioblastoma) and animal models (atherosclerosis, pulmonary hypertension).

Main Results:

  • Identified MANTIS (lncRNA n342419) as a key epigenetically regulated lncRNA.
  • MANTIS expression is altered in pulmonary hypertension, atherosclerosis, and glioblastoma.
  • MANTIS deletion/silencing impairs endothelial cell angiogenesis and shear stress response.
  • MANTIS interacts with BRG1 to regulate chromatin remodeling and transcription of key endothelial genes (SOX18, SMAD6, COUP-TFII).

Conclusions:

  • MANTIS is a novel, differentially regulated lncRNA.
  • MANTIS plays a critical role in facilitating endothelial angiogenic function.
  • MANTIS represents a potential therapeutic target for vascular diseases.