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MicroRNA‑93 regulates angiogenesis in peripheral arterial disease by targeting CDKN1A

Xiaojun Shu1, Youjun Mao2, Zhengfei Li1

  • 1Department of Interventional Radiology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.

Molecular Medicine Reports
|May 7, 2019
PubMed

Insights

MicroRNA-93 (miR-93) promotes blood vessel growth in peripheral arterial disease (PAD) by inhibiting CDKN1A. This miR-93/CDKN1A pathway offers a new therapeutic target for PAD angiogenesis.

Area of Science:

  • Molecular Biology
  • Vascular Biology
  • Oncology

Background:

  • MicroRNAs (miRNAs) regulate gene expression and are implicated in tumor progression.
  • The role of miRNAs in ischemia-induced angiogenesis, particularly in peripheral arterial disease (PAD), is not well understood.
  • The specific mechanisms by which miRNAs influence PAD pathogenesis remain largely unknown.

Purpose of the Study:

  • To investigate the role and mechanism of microRNA-93 (miR-93) in ischemia-induced angiogenesis in PAD.
  • To identify potential molecular targets of miR-93 involved in angiogenesis.
  • To evaluate the therapeutic potential of modulating miR-93 in a preclinical PAD model.

Main Methods:

  • Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to measure miR-93 expression in PAD patients and endothelial cells.
  • In vitro assays to assess the effects of miR-93 on endothelial cell proliferation, migration, and tube formation.
  • Western blotting and RT-qPCR to analyze the expression of target genes, including CDKN1A.
  • A hind-limb ischemia mouse model to evaluate the in vivo effects of miR-93 on angiogenesis and perfusion recovery.

Main Results:

  • miR-93 was significantly upregulated in PAD patients and hypoxia-exposed endothelial cells.
  • Overexpression of miR-93 promoted endothelial cell proliferation, migration, and tube formation, indicating enhanced angiogenesis.
  • miR-93 directly inhibited the expression of Cyclin dependent kinase 1A (CDKN1A) at both mRNA and protein levels.
  • In vivo, miR-93 overexpression improved capillary density and accelerated perfusion recovery in a hind-limb ischemia model.

Conclusions:

  • miR-93 plays a crucial role in promoting angiogenesis in the context of PAD.
  • The miR-93/CDKN1A pathway represents a novel mechanism regulating angiogenesis in PAD.
  • miR-93 is a potential therapeutic target for promoting angiogenesis and treating PAD.

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