LncEGFL7OS regulates human angiogenesis by interacting with MAX at the EGFL7/miR-126 locus.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30741632.
- Also identified by DOI 10.7554/eLife.40470 and PMC identifier 6370342.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
In an effort to identify human endothelial cell (EC)-enriched lncRNAs,~500 lncRNAs were shown to be highly restricted in primary human ECs. Among them, <i>lncEGFL7OS</i>, located in the opposite strand of the <i>EGFL7/miR-126</i> gene, is regulated by ETS factors through a bidirectional promoter in ECs. It is enriched in highly vascularized human tissues, and upregulated in the hearts of dilated cardiomyopathy patients. LncEGFL7OS silencing impairs angiogenesis as shown by EC/fibroblast co-culture, in vitro/in vivo and ex vivo human choroid sprouting angiogenesis assays, while lncEGFL7OS overexpression has the opposite function. Mechanistically, lncEGFL7OS is required for MAPK and AKT pathway activation by regulating EGFL7/miR-126 expression. MAX protein was identified as a lncEGFL7OS-interacting protein that functions to regulate histone acetylation in the EGFL7/miR-126 promoter/enhancer. CRISPR-mediated targeting of EGLF7/miR-126/lncEGFL7OS locus inhibits angiogenesis, inciting therapeutic potential of targeting this locus. Our study establishes lncEGFL7OS as a human/primate-specific EC-restricted lncRNA critical for human angiogenesis.
Medical subject headings
- Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
- Calcium-Binding Proteins
- EGF Family of Proteins
- Genetic Loci
- MicroRNAs
- RNA, Long Noncoding