Title
LncEGFL7OS Regulates Human Angiogenesis by Interacting with MAX at the EGFL7/miR-126 Locus
Funding Source
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
Grant Number
2 T34GM007716-38,2G12MD007595-06, EY026069,EY021862, 2G12MD007595-07
Department
Department of Biology
Document Type
Article
Publication Date
2-2019
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, 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.
Recommended Citation
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.
https://digitalcommons.xula.edu/fac_pub/191
Comments
DOI: 10.7554/eLife.40470
PubMed ID: 30741632
Funding text
We thank Ms. Joy Roussel, Mr. Adam Leimer and other members from Southern Eye Bank for their generous support. We thank Dr. Ming Zhan from Houston Methodist Research Institute for help and discussion of the microarray data, Dr. Joseph Miano from University of Rochester Medical Center for help in RNA FISH experiments, and Dr. Frank Jones from Tulane University for sharing equipment. SW was supported by a startup fund from Tulane University, NIH Grants EY021862 and EY026069, a career development award from the Research to Prevent Blindness foundation, and a Bright Focus Foundation Award in Age-related Macular Degeneration. QZ was supported by an American Heart Association (AHA) postdoctoral fellowship. KZ was supported by grant 2G12MD007595-07 from National Institute on Minority Health and Health Disparities (NIMHD), NIH and Department of Health and Human Services (DHHS). P B was supported by 2G12MD007595-06 from NIMHD, NIH diversity consortium program/Building Infrastructure Leading to Diversity (BUILD)−2 T34GM007716-38.