Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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MiR-199a/b-5p Inhibits Lymphangiogenesis by Targeting Discoidin Domain Receptor 1 in Corneal Injury

  • Oh, Sooeun (Department of Medical Lifescience, College of Medicine, The Catholic University of Korea) ;
  • Seo, Minkoo (Department of Medical Lifescience, College of Medicine, The Catholic University of Korea) ;
  • Choi, Jun-Sub (Catholic Institute for Visual Science, College of Medicine, The Catholic University of Korea) ;
  • Joo, Choun-Ki (Catholic Institute for Visual Science, College of Medicine, The Catholic University of Korea) ;
  • Lee, Suk Kyeong (Department of Medical Lifescience, College of Medicine, The Catholic University of Korea)
  • Received : 2017.08.11
  • Accepted : 2017.11.10
  • Published : 2018.02.28
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Abstract

Discoidin domain receptor 1 (DDR1) is involved in tumorigenesis and angiogenesis. However, its role in lymphangiogenesis has been unknown. Here, we tested whether downregulation of DDR1 expression by miR-199a/b can suppress lymphangiogenesis. We also aimed to identify miRNA target site(s) in the 3' untranslated region (UTR) of DDR1. Transfection with miR-199a/b-5p mimics reduced expression of DDR1 and tube formation in primary human dermal lymphatic endothelial cells, whereas miR-199a/b-5p inhibitors showed the opposite effects. Critically, injection of miR-199a/b-5p mimics suppressed DDR1 expression and lymphangiogenesis in a corneal alkali-burn rat model. The three well-conserved seed matched sites for miR-199a/b-5p in the DDR1 3'-UTR were targeted, and miRNA binding to at least two sites was required for DDR1 inhibition. Our data suggest that DDR1 promotes enhanced lymphangiogenesis during eye injury, and miR-199a/b-5p suppresses this activity by inhibiting DDR1 expression. Thus, this miRNA may be useful for the treatment of lymphangiogenesis-related eye diseases.

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References

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