Journal
PLOS ONE
Volume 13, Issue 3, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0193590
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Funding
- National Institutes of Health/NEI [R01EY17950]
- Research to Prevent Blindness, New York, NY [RPB 2017]
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Short-activating RNA (saRNA), which targets gene promoters, has been shown to increase the target gene expression. In this study, we describe the use of an saRNA (Flt a-1) to target the flt-1 promoter, leading to upregulation of the soluble isoform of Flt-1 and inhibition of angiogenesis. We demonstrate that Flt a-1 increased sFlt-1 mRNA and protein levels, while reducing VEGF expression. This was associated with suppression of human umbilical vascular endothelial cell (HUVEC) proliferation and cell cycle arrest at the G(0)/G(1) phase. HUVEC migration and tube formation were also suppressed by Flt a-1. An siRNA targeting Flt-1 blocked the effects of Flt a-1. Flt a-1 effects were not mediated via argonaute proteins. However, trichostatin A and 5'-deoxy-5'-(methylthio) adenosine inhibited Flt a-1 effects, indicating that histone acetylation and methylation are mechanistically involved in RNA activation of Flt-1. In conclusion, RNA activation of sFlt-1 can be used to inhibit angiogenesis.
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