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Shusheng Wang, Qinbo Zhou, Jing Ma, Bo Yu; lncEGFL7OS regulates human ocular angiogenesis via cis and trans regulatory mechanisms. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5488. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Identifying regulatory mechanism for human angiogenesis is crucial for developing angiogenic therapies that are readily translatable in humans. The role of long noncoding RNAs (lncRNA) in human ocular angiogenesis is largely unknown. We have recently identified a list of endothelial cell (EC)-enriched lncRNAs by gene profiling study. Among them, lncEGFL7OS was confirmed to have a critical role in human choroidal angiogenesis. The purpose of the current project is to further study its function and mechanism.
RNA interference and adenovirus overexpression, in conjunction with choroid sprouting assays, were employed to study the lncRNA functional mechanism in trans; while a CRISPR/Cas9 system and human embryonic stem cells (hES) were harnessed to study its mechanism in cis. Matrigel and EC/fibroblast co-culture angiogenesis assays were used to further determine its role in angiogenesis using the systems above.
Consistent with our previous results using other models, lncEGFL7OS silencing in ECs results in impaired angiogenesis in an EC/fibroblast co-culture angiogenesis model. CRISPR/dCas9 system targeted repression of lncEGFL7OS leads to downregulation of its regulated gene miR-126, suggesting the existence of cis regulatory mechanism of lncEGFL7OS function. On the contrary, lncEGFL7OS overexpression promotes angiogenesis in both EC/fibroblast co-culture model and mouse choroid branching model, suggesting that lncEGFL7OS may function in trans manner. Currently, a CRISPR-based knockout system is used to verify the functional mechanism of lncEGFL7 in ECs.
lncEGFL7OS regulates angiogenesis via both cis and trans mechanisms, which may have implications in human angiogenesis-related diseases, including age-related macular degeneration.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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