Strand and cell type-specific function of microRNA-126 in angiogenesis

Qinbo Zhou, Chastain Anderson, Jakub Hanus, Fangkun Zhao, Jing Ma, Akihiko Yoshimura, Shusheng Wang

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

microRNAs or miRs have been shown to be pivotal modulators of vascular development. The strand and cell type-specific function of miR-126 in angiogenesis, especially pathological angiogenesis, remains poorly defined. We characterized the retinal vascular phenotype of miR-126-/- mice, and tested the function of miR-126 strands (miR-126-3p and -5p) using in vitro angiogenesis models and a mouse model of neovascular age-related macular degeneration. We found that miR-126 is critical for retinal vascular development but has dual function in pathological angiogenesis. miR-126-/- mice showed defective postnatal retinal vascular development and remodeling, which is partially rescued by genetic knockout of its target gene Spred-1. Surprisingly, either silencing miR-126-3p by LNA-antimiR or overexpressing miR-126-3p by miRNA mimic repressed laser-induced choroidal neovascularization. To dissect the underlying mechanism, we found in endothelial cells, silencing of miR-126-3p repressed angiogenesis, while overexpression of miR-126-5p enhanced angiogenesis. However, in retinal pigment epithelial cells, miR-126-3p repressed vascular endothelial growth factor (VEGF-A) expression via a novel mechanism of regulating αB-Crystallin promoter activity and by directly targeting VEGF-A 3′-untranslated region. These findings provide first genetic evidence that miR-126 is required for the development of different retinal vascular layers, and also uncover a strand and cell type-specific function of miR-126 in ocular pathological angiogenesis.

Original languageEnglish
Pages (from-to)1823-1835
Number of pages13
JournalMolecular Therapy
Volume24
Issue number10
DOIs
Publication statusPublished - 2016 Oct 1

    Fingerprint

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

Zhou, Q., Anderson, C., Hanus, J., Zhao, F., Ma, J., Yoshimura, A., & Wang, S. (2016). Strand and cell type-specific function of microRNA-126 in angiogenesis. Molecular Therapy, 24(10), 1823-1835. https://doi.org/10.1038/mt.2016.108