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Updated: Jun 30, 2026
11:44
Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
miR-486-5p Inhibits eNOS and Angiogenesis in Cultured Endothelial Cells by Targeting MAML3.
Adrianna Douvris1,2, Ali Maadelat1, Christopher J Porter3
1Division of Nephrology, Department of Medicine and Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
Journal of Cellular and Molecular Medicine
|May 28, 2025
Summary
MicroRNA-486-5p protects against kidney injury by inhibiting endothelial nitric oxide synthase (eNOS) and angiogenesis. This process involves targeting MAML3, revealing a new pathway regulating endothelial cell function.
Area of Science:
- Endocrinology and Metabolism
- Molecular Biology
- Cell Biology
Background:
- Kidney ischemia-reperfusion (I/R) injury is linked to endothelial damage.
- MicroRNA (miR)-486-5p shows protective effects in rat kidney I/R injury.
- miR-486-5p localizes to capillary endothelial cells but inhibits endothelial nitric oxide synthase (eNOS) protein expression.
Purpose of the Study:
- To investigate the impact of miR-486-5p on eNOS and endothelial cell function.
- To identify the messenger RNA (mRNA) targets of miR-486-5p.
- To elucidate the molecular mechanisms underlying miR-486-5p's effect on angiogenesis.
Main Methods:
- Human umbilical vein endothelial cells (HUVECs) were transfected with miR-486-5p mimic.
- Assays included proliferation, migration, and network formation.
- Biotinylated miR-486-5p pulldown followed by RNA sequencing identified mRNA targets.
Main Results:
- miR-486-5p significantly reduced eNOS mRNA and protein levels in HUVECs and pulmonary microvascular endothelial cells.
- Angiogenesis was inhibited by miR-486-5p, an effect reversed by eNOS plasmid transfection.
- RNA sequencing identified FOXO1, FOXP1, TNFSF4, MAML3, CELSR3, and SPCS2 as miR-486-5p targets; MAML3 silencing inhibited eNOS.
Conclusions:
- miR-486-5p inhibits endothelial cell angiogenesis through eNOS down-regulation.
- This inhibitory effect is mediated by the selective targeting of MAML3.
- The study reveals a novel pathway regulating endothelial cell function via miR-486-5p and MAML3.
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