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Updated: Jun 30, 2026

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
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
PubMed

Insights

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.
Keywords:
RNA‐sequencingangiogenesisendothelial cellsmiRNAmiRNA pulldown

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