LncEGFL7OS Regulates Human Angiogenesis by Interacting with MAX at the EGFL7/miR-126 Locus
National Institute on Minority Health and Health Disparities, U.S. Department of Health and Human Services, National Institutes of Health, Research to Prevent Blindness, American Heart Association
2 T34GM007716-38,2G12MD007595-06, EY026069,EY021862, 2G12MD007595-07
Department of Biology
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, lncEGFL7OS, located in the opposite strand of the EGFL7/miR-126 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.
Zhou, Q.; Yu, B.; Anderson, C.; Huang, Z.-P.; Zhang, Wensheng; Han, Y.; Bhattacharjee, Partha S.; Srinivasan, S.; Zhang, Kun; Wang, D.-Z.; and Wang, S., "LncEGFL7OS Regulates Human Angiogenesis by Interacting with MAX at the EGFL7/miR-126 Locus" (2019). Faculty and Staff Publications. 191.