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  • Title: VEGF-mediated angiogenesis in retinopathy of prematurity is co-regulated by miR-17-5p and miR-20a-5p.
    Author: Guo Y, Du F, Tan YL, Luo J, Xiong D, Song WT.
    Journal: Biochem Cell Biol; 2021 Aug; 99(4):414-423. PubMed ID: 34319836.
    Abstract:
    The microRNAs miR-17-5p and miR-20a-5p play important roles on angiogenesis; however, it is arguable whether they regulate the formation of retinal blood vessels in retinopathy of prematurity (ROP). We used a mouse model of oxygen-induced retinopathy (OIR) to simulate the development of retinas in mice suffering from ROP, and the expression levels of miR-20a-5p, miR-17-5p, hypoxia-inducible factor 1-alpha (HIF-1α), and vascular endothelial growth factor (VEGF) were measured by RT-qPCR and Western blotting. Cell proliferation, apoptosis, and angiogenesis in the OIR model mice were measured using MTT assays, flow cytometry, and Matrigel assays, respectively. The interaction between HIF-1α/VEGF and miR-20a-5p/miR-17-5p were further validated using dual-luciferase reporter assays, biotin-labeled RNA-pulldown, and RNA immunoprecipitation (RIP) assays. In our OIR model, retinal angiogenesis in the mice was associated with down-regulation of miR-20a-5p and miR-17-5p, as well as up-regulation of HIF-1α and VEGF. In addition, the miR-20a-5p and miR-17-5p inhibited cell proliferation and angiogenesis through regulating HIF-1α and VEGF in the retinal cells of the OIR model mice. Moreover, it was found that miR-20a-5p and miR-17-5p bind to HIF-1α and VEGF at the 3'UTR, and there was a combined effect between miR-20a-5p and miR-17-5p on the regulation of HIF-1α and VEGF. It is worth noting that miR-17-5p and miR-20a-5p can preferentially regulate HIF-1α, then act on VEGF, thereby affecting the angiogenesis associated with ROP.
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