Related Experiment Video
Updated: Jun 6, 2026
A Simplified Technique for Producing an Ischemic Wound Model
Published on: May 2, 2012
Circular RNAs in Diabetic Foot Ulcers: A Scoping Review of Clinical, Preclinical, and In Silico Evidence on
Amir Reza Ghafourian1,2, Masoomeh Hamdi1,2, Atefeh Soltan Mohseni1,2
1Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran.
Background And Objective:
Diabetic foot ulcers (DFUs) involve chronic inflammation, impaired angiogenesis, oxidative stress, and disrupted fibroblast-keratinocyte interactions. Circular RNAs (circRNAs), a category of stable non-coding RNAs, have become essential regulators of these processes; nevertheless, their comprehensive functions in DFUs are still inadequately characterised. This scoping review integrated clinical, preclinical, and in silico evidence on circRNAs in DFUs to assess their diagnostic, mechanistic, and therapeutic potential.
Methods:
Systematic searches of MEDLINE, EMBASE, Web of Science, and Google Scholar were conducted on July 16, 2025, according to the PRISMA-ScR guidelines. Eligible papers included clinical investigations of circRNAs in the tissues of patients with DFUs, preclinical animal models assessing circRNA-based therapies, and computational predictions of circRNA-miRNA-mRNA networks. Information was collected on circRNA expression, molecular targets, clinical associations, and therapeutic effects.
Results:
Twenty-two studies (7 clinical, 13 preclinical, 2 in silico) were selected. Clinical studies found hsa_circ_PRKDC, hsa_circ_072697, hsa_circ_080968, and hsa_circ_0000907 to be associated with wound severity, tissue perfusion, and keratinocyte proliferation in patients with diabetic foot ulcers. Preclinical studies showed that delivery of mmu_circHIPK3, mmu_circMYO9B, and mmu_circ_Astn1 via exosomes or nanoparticles improved angiogenesis, epithelial regeneration, and wound closure. However, the silence of mmu_circ_0005654 reduced ferroptosis and inflammation. In silico analyses identified potential regulatory axes, such as hsa_circ_0089761/miR-146a-5p/SMAD4 (Mothers against decapentaplegic homologue 4) and hsa_circ_0049271/miR-24-3p/JUNB, that were associated with inflammatory-angiogenic pathways in this disease.
Conclusions:
CircRNAs hold promise for the diagnosis and treatment of DFUs by modulating angiogenesis, inflammation, oxidative stress, and epithelial repair. Standard network-guided therapies are essential to translate circRNA-based strategies into clinical practice.
Insights
Circular RNAs (circRNAs) show promise for diagnosing and treating diabetic foot ulcers (DFUs) by regulating key healing processes. Further research into network-guided therapies is needed for clinical application.
Area of Science:
- Molecular Biology
- Genomics
- Regenerative Medicine
Background:
- Diabetic foot ulcers (DFUs) are complex wounds characterized by chronic inflammation, impaired angiogenesis, oxidative stress, and disrupted cell interactions.
- Circular RNAs (circRNAs) are emerging as critical regulators of these pathological processes in DFUs.
- The comprehensive role of circRNAs in DFUs remains incompletely understood, necessitating a review of current evidence.
Purpose of the Study:
- To conduct a scoping review integrating clinical, preclinical, and in silico evidence on circRNAs in DFUs.
- To assess the diagnostic, mechanistic, and therapeutic potential of circRNAs in the context of diabetic foot ulcers.
- To identify key circRNAs and their regulatory networks involved in DFU pathogenesis.
Main Methods:
- Systematic literature searches were performed across multiple databases (MEDLINE, EMBASE, Web of Science, Google Scholar) following PRISMA-ScR guidelines.
- Included studies encompassed clinical investigations, preclinical animal models of circRNA-based therapies, and computational predictions of circRNA-miRNA-mRNA networks.
- Data extraction focused on circRNA expression, molecular targets, clinical associations, and therapeutic effects in DFUs.
Main Results:
- Seven clinical studies identified specific circRNAs (e.g., hsa_circ_PRKDC) associated with DFU severity and keratinocyte proliferation.
- Thirteen preclinical studies demonstrated that exosome/nanoparticle-delivered circRNAs (e.g., mmu_circHIPK3) enhanced angiogenesis and wound healing, while silencing others (e.g., mmu_circ_0005654) reduced inflammation.
- In silico analyses revealed potential regulatory axes (e.g., hsa_circ_0089761/miR-146a-5p/SMAD4) involved in inflammatory-angiogenic pathways relevant to DFUs.
Conclusions:
- Circular RNAs exhibit significant potential for the diagnosis and treatment of diabetic foot ulcers.
- CircRNAs can modulate critical pathways including angiogenesis, inflammation, oxidative stress, and epithelial repair in DFUs.
- Translating circRNA-based strategies into clinical practice requires standardized network-guided therapeutic approaches.
