Funding Source

National Institute on Minority Health and Health Disparities, National Institutes of Health (BUILD), National Eye Institute

Grant Number

2G12MD007595-06, (BUILD)-2T34GM007716-38, 2G12MD007595-07, EY021862, EY026069


Department of Biology

Document Type


Publication Date



In an effort to identify human endothelial cell (EC)-enriched lncRNAs,~500 lncRNAswere shown to be highly restricted in primary human ECs. Among them,lncEGFL7OS, located inthe opposite strand of theEGFL7/miR-126gene, is regulated by ETS factors through abidirectional promoter in ECs. It is enriched in highly vascularized human tissues, and upregulatedin the hearts of dilated cardiomyopathy patients. LncEGFL7OS silencing impairs angiogenesis asshown by EC/fibroblast co-culture, in vitro/in vivo and ex vivo human choroid sproutingangiogenesis assays, while lncEGFL7OS overexpression has the opposite function. Mechanistically,lncEGFL7OS is required for MAPK and AKT pathway activation by regulating EGFL7/miR-126expression. MAX protein was identified as a lncEGFL7OS-interacting protein that functions toregulate histone acetylation in the EGFL7/miR-126 promoter/enhancer. CRISPR-mediated targetingof EGLF7/miR-126/lncEGFL7OS locus inhibits angiogenesis, inciting therapeutic potentialargeting this locus. Our study establishes lncEGFL7OS as a human/primate-specific EC-restricted lncRNA critical for human angiogenesis.