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miR‑205: A dual regulator of angiogenesis in health and disease (Review)

  • Authors:
    • Maria Oltra
    • Miriam Martínez‑Santos
    • Maria Ybarra
    • Maria Pires
    • Chiara Ceresoni
    • Clara Gomis‑Coloma
    • Cristina Medina‑Trillo
    • Javier Sancho
    • Jorge Barcia
  • View Affiliations / Copyright

    Affiliations: Faculty of Medicine and Health Sciences, Universidad Católica de Valencia San Vicente Mártir, 46001 Valencia, Spain
    Copyright: © Oltra et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 51
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    Published online on: December 29, 2025
       https://doi.org/10.3892/ijmm.2025.5722
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Abstract

The present study evaluated the role of microRNA (miR)‑205 as a dual regulator of angiogenesis, exhibiting both pro‑angiogenic and anti‑angiogenic effects depending on the biological context. miRs are small non‑coding sequences that regulate gene expression at the post‑transcriptional level and can be transported in extracellular vesicles (EVs), allowing them to modulate biological processes remotely. miR‑205 is involved in multiple cellular processes, such as proliferation, migration, apoptosis and angiogenesis. In angiogenesis its function is contradictory: On one hand, it can inhibit blood vessel formation by suppressing pro‑angiogenic factors such as VEGF and ANG‑2, as demonstrated in diseases such as psoriasis, thyroid cancer and diabetic retinopathy. However, in other contexts, miR‑205 promotes angiogenesis by inhibiting anti‑angiogenic genes such as PTEN and HITT, facilitating the activation of the PI3K/AKT pathway and cell proliferation in ovarian cancer and thrombosis. Additionally, the present study highlighted the role of EVs in transferring miR‑205 between cells, thereby influencing angiogenesis and disease progression. Studies in myocardial infarction and cancer models have demonstrated that EVs enriched in miR‑205 can affect blood vessel formation and tumor progression. Similarly, in ocular diseases such as macular degeneration and diabetic retinopathy, miR‑205 encapsulated in EVs has shown therapeutic potential by regulating VEGF levels. In conclusion, miR‑205 emerges as a promising therapeutic target for angiogenic diseases. Its application in EV‑based therapy could represent an innovative strategy for treating vascular disorders. However, further studies are needed to fully understand its mechanisms of action and optimize its clinical application.
View Figures

Figure 1

miR-205 transcriptional and
posttranscriptional regulation. Created in https://BioRender.com. miR, microRNA; TWIST1,
Twist-related protein 1; Sp1, Specifiticy protein 1; p53, Tumor
protein p53; HIF-1α, Hypoxia-inducible factor 1-alpha; lncRNA, long
non-coding RNA; LINC00673, Long intergenic non-protein coding RNA
673; GAS5, Growth arrest-specific 5; MALAT-1, Metastasis-associated
lung adenocarcinoma transcript 1; SNHG5, Small nucleolar RNA host
gene 5; ZEB1-AS1, Zing finger E-box binding homebox 1 antisense RNA
1.

Figure 2

Representation of the main regulatory
pathways of angiogenesis and the targets of miR-205. The direct
targets of miR-205 are highlighted in purple. Created in https://BioRender.com. miR, microRNA; VEGFA, vascular
endothelial growth factor A; VEGFR-2, vascular endothelial growth
factor receptor 2; TGFβR, transforming growth factor β receptor;
PI3K, phosphoinositide 3-kinase; Akt, protein kinase B; mTOR,
mechanistic target of rapamycin; RAS, rat sarcoma viral oncogene
homolog; RAI, Ras-associated/activated inhibitor; MEK,
mitogen-activated protein kinase kinase; ERK, extracellular
signal-regulated kinase; MAPK, mitogen-activated protein kinase;
JAK, Janus kinase; STAT, signal transducer and activator of
transcription; PTEN, phosphatase and tensin homolog; HIF-1α,
hypoxia-inducible factor 1-alpha; TF, transcription factor; MiCAL2,
microtubule-associated monooxygenase, calponin and LIM
domain-containing 2; HiTT, HIF-1α inhibitor at the transcriptional
level (lncRNA); YAP-1, yes-associated protein 1; SMAD, SMAD
signaling proteins; ANG2, angiopoietin-2; MMP2/9, matrix
metalloproteinases 2 and 9; IL-11, interleukin-11; IL-5,
interleukin-5; VEGF, vascular endothelial growth factor.

Figure 3

Representation of the 3'UTR targets
of miR-205. Targets acting as anti-angiogenic factors are shown in
green, and pro-angiogenic ones in red. Direct targets, defined by
miR-205 binding to the 3'UTR region, are depicted as circles, while
indirect targets of miR-205 are depicted as squares. miR-205,
microRNA-205; ANG-2, angiopoietin-2; AMOT, angiomotin; CCNB2,
cyclin B2; CDH11, cadherin-11; FGF1, fibroblast growth factor 1;
HIF-1α, hypoxia-inducible factor 1-alpha; HiTT, HIF-1α inhibitor at
the transcriptional level; KLF12, Krüppel-like factor 12; MiCAL2,
microtubule-associated monooxygenase, calponin and LIM
domain-containing 2; NOTCH2, neurogenic locus notch homolog protein
2; PTEN, phosphatase and tensin homolog; SMAD2, mothers against
decapentaplegic homolog 2; SMAD4, mothers against decapentaplegic
homolog 4; VEGFA, vascular endothelial growth factor A; YAP1,
yes-associated protein 1; 3'-UTR, 3'-untranslated region.

Figure 4

KEGG pathway enrichment of
miR-205-regulated genes. Dots represent enriched pathways; x-axis:
Fold Enrichment; dot size: number of genes; dot color:
-log10(FDR). The top pathways (Hippo/YAP1,
PI3K-Akt/PTEN, TGF-β/SMAD, p53/EGFR resistance, AGE-RAGE in
diabetic complications) highlight canonical mechanisms by which
miR-205 can exert anti- or pro-angiogenic effects depending on the
targeted nodes and context. KEGG Kyoto Encyclopedia of Genes and
Genomes; FDR, false discovery rate; miR-205, microRNA-205;
PI3K-Akt, phosphoinositide 3-kinase-protein kinase B; TGF-β,
transforming growth factor-β; EGFR, epidermal growth factor
receptor; HPV, human papillomavirus; AGE-RAGE, advanced glycation
end products-receptor for advanced glycation end products.
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Copy and paste a formatted citation
Spandidos Publications style
Oltra M, Martínez‑Santos M, Ybarra M, Pires M, Ceresoni C, Gomis‑Coloma C, Medina‑Trillo C, Sancho J and Barcia J: miR‑205: A dual regulator of angiogenesis in health and disease (Review). Int J Mol Med 57: 51, 2026.
APA
Oltra, M., Martínez‑Santos, M., Ybarra, M., Pires, M., Ceresoni, C., Gomis‑Coloma, C. ... Barcia, J. (2026). miR‑205: A dual regulator of angiogenesis in health and disease (Review). International Journal of Molecular Medicine, 57, 51. https://doi.org/10.3892/ijmm.2025.5722
MLA
Oltra, M., Martínez‑Santos, M., Ybarra, M., Pires, M., Ceresoni, C., Gomis‑Coloma, C., Medina‑Trillo, C., Sancho, J., Barcia, J."miR‑205: A dual regulator of angiogenesis in health and disease (Review)". International Journal of Molecular Medicine 57.2 (2026): 51.
Chicago
Oltra, M., Martínez‑Santos, M., Ybarra, M., Pires, M., Ceresoni, C., Gomis‑Coloma, C., Medina‑Trillo, C., Sancho, J., Barcia, J."miR‑205: A dual regulator of angiogenesis in health and disease (Review)". International Journal of Molecular Medicine 57, no. 2 (2026): 51. https://doi.org/10.3892/ijmm.2025.5722
Copy and paste a formatted citation
x
Spandidos Publications style
Oltra M, Martínez‑Santos M, Ybarra M, Pires M, Ceresoni C, Gomis‑Coloma C, Medina‑Trillo C, Sancho J and Barcia J: miR‑205: A dual regulator of angiogenesis in health and disease (Review). Int J Mol Med 57: 51, 2026.
APA
Oltra, M., Martínez‑Santos, M., Ybarra, M., Pires, M., Ceresoni, C., Gomis‑Coloma, C. ... Barcia, J. (2026). miR‑205: A dual regulator of angiogenesis in health and disease (Review). International Journal of Molecular Medicine, 57, 51. https://doi.org/10.3892/ijmm.2025.5722
MLA
Oltra, M., Martínez‑Santos, M., Ybarra, M., Pires, M., Ceresoni, C., Gomis‑Coloma, C., Medina‑Trillo, C., Sancho, J., Barcia, J."miR‑205: A dual regulator of angiogenesis in health and disease (Review)". International Journal of Molecular Medicine 57.2 (2026): 51.
Chicago
Oltra, M., Martínez‑Santos, M., Ybarra, M., Pires, M., Ceresoni, C., Gomis‑Coloma, C., Medina‑Trillo, C., Sancho, J., Barcia, J."miR‑205: A dual regulator of angiogenesis in health and disease (Review)". International Journal of Molecular Medicine 57, no. 2 (2026): 51. https://doi.org/10.3892/ijmm.2025.5722
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