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Cited by 55MicroRNA in disease regulationBarrier Structure and Function StudiesAngiogenesis and VEGF in Cancer

The Poly-cistronic miR-23-27-24 Complexes Target Endothelial Cell Junctions: Differential Functional and Molecular Effects of miR-23a and miR-23b

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Li, Jia, Zhao, Yang, Lu, Ying, Ritchie, William, Grau, Georges, Vadas, Mathew A, Gamble, Jennifer R·2016·Molecular Therapy - Nucleic Acids
DOI 10.1038/mtna.2016.62PMC PMC5023406
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Abstract

The regulation of function of endothelial cell-cell junctions is fundamental in sustaining vascular integrity. The polycistronic microRNA (miR) complexes containing miR-23a-27a-24-2, and 23b-27b-24-1 are predicted to target the majority of major endothelial junctional proteins. We focus on miR-23a and miR-23b, and investigate the functional effects of these miRs on junctions. While miR-23a and 23b only differ by 1 nucleotide (g19) outside the seed region and thus are predicted to have the same targets, they function differently with miR-23a inhibiting permeability and miR-23b inhibiting angiogenesis. Both miRs target the junctional attractive molecule (tight junction protein 2) ZO-2 and the repulsive molecule junctional adhesion molecule C (JAM-C), although the inhibition of JAM-C by miR-23a is more profound than by miR-23b. The difference in potency is attributable to differences at g19 since a mutation of the t17, the g19 binding site of miR-23b in the 3'UTR of JAM-C restores identity. We also show that the pattern of expression of miR-23a and miR-23b and their targets are different. Thus, the paralogues miR-23a and miR-23b can have profoundly different effects on endothelial cell function due at least partially to selective effects on target proteins and differences in expression patterns of the miRs. This work exposes a hitherto unappreciated complexity in therapeutically targeting miRs.

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  • miR-23a mainly acts on permeability-related proteins, while miR-23b displays inhibition of angiogenesis by blocking cell cycle progression and reducing endothelial cell rejection signals.

    “Specifically, miR-23a mainly acts on permeability-related proteins, while miR-23b displays inhibition of angiogenesis by blocking cell cycle progression and reducing endothelial cell rejection signals [44,45].”

    From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [44]

    The Results sections on vascular permeability and angiogenesis report that miR-23a affects endothelial junctions and permeability, while miR-23b inhibits angiogenesis. The cited passages do not establish that miR-23b does so by blocking cell-cycle progression or reducing endothelial-cell rejection signals; the paper discusses repulsive junctional proteins, but not those proposed mechanisms. Page numbers are unavailable in our copy. (LLM, conf=0.87)

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Authors
Li, J., Zhao, Y., Lu, Y., Ritchie, W., Grau, G., Vadas, M. A., & Gamble, J. R.
Affiliations
The University of Sydney (AU)
Corresponding author
  • Vadas, Mathew A
  • Gamble, Jennifer R
ORCID
Venue
Molecular Therapy - Nucleic Acids
Publisher
Elsevier BV
Published
2016
Volume
5
Issue
8
Pages
e354
ISSN
2162-2531 (ISSN-L)
DOI
10.1038/mtna.2016.62
PMC
PMC5023406
OpenAlex
W2511855771
Cited by
55
References
53
Citations by year
2026: 3 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 7 · 2020: 9 · 2019: 7 · 2018: 12 · 2017: 7
FWCI
3.61
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Therapy — Nucleic Acids (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Medical Research Council
  • National Health and Medical Research Council (349332)
  • Sydney Medical School
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Keywords
miR-23a, miR-23b, endothelial junctions, tight junctions, vascular permeability, angiogenesis, ZO-2, JAM-C, 3' UTR binding, microRNA target regulation

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