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MiR‐9 Promotes Angiogenesis via Targeting on Sphingosine‐1‐Phosphate Receptor 1
Author(s) -
Zeng Ye,
Yao Xinghong
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.01721
Subject(s) - s1pr1 , angiogenesis , cancer research , sphingosine 1 phosphate , biology , sphingosine , vasculogenesis , neovascularization , microrna , chemistry , receptor , endothelial stem cell , microbiology and biotechnology , vascular endothelial growth factor a , vascular endothelial growth factor , biochemistry , in vitro , vegf receptors , gene
We previously demonstrated that vascular endothelial cells released VEGF‐enriched exosomes to promote the tumor vasculogenesis and progression after anti‐angiogenic therapies (AATs). To clarify how microRNA (miR)‐9 promoted the angiogenesis of tumoral endothelial cells (TECs), in the present study, we investigated the association between miR‐9 and sphingosine‐1‐phosphate (S1P) receptors in angiogenesis. The levels of miR‐9 and S1P receptors (S1PRs) and their correlations in various normal and tumoral endothelial cells were analyzed. The endothelial cells overexpressing miR‐9 were used as cell model of TECs. The levels of S1PR1, S1PR2, and S1PR3 were detected in the TECs by qRT‐PCR and western blot. The binding sites of miR‐9 on S1PR1 and S1PR3 were predicted and tested by dual‐luciferase reporter assays. Then, angiogenesis in endothelial cells overexpressing both S1PR1 and miR‐9 was detected. The results showed that miR‐9 is overexpressed in ECs from medulloblastoma and glioblastoma xenograft, which is negatively associated with S1PR1 and S1PR3. Overexpression of miR‐9 significantly inhibited S1PR1 and S1PR3 in both mRNA and protein levels. We predicted that binding sites exist between miR‐9 and S1PR1, S1PR3, but only S1PR1 was directly targeted by miR‐9. Overexpression of S1PR1 significantly suppressed the miR‐9‐induced angiogenesis. Therefore, miR‐9 induces angiogenesis via targeting on S1PR1. We proposed that renormalization of TECs would be a more efficient cancer therapy than the current AATs.