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Conserved Hypoxia-Responsive miRNA Programs Define Adaptive and Stress-Limiting Regulatory Axes in Hepatocellular
Most Shumi Akhter Shathi1, Mohammad Arif1,2, Nobuhiro Nozaki1
1Joint Graduate School of Veterinary Medicine, Kagoshima University, Kagoshima 890-8580, Japan.
Cells
|August 13, 2026
Summary
Researchers identified hypoxia-responsive microRNAs (HRMs) in canine liver cancer. Two specific HRMs, cfa-miR-210 and cfa-miR-34a, show potential as circulating biomarkers for hepatocellular carcinoma (HCC) diagnosis.
Area of Science:
- Comparative oncology
- Molecular biology
- Biomarker discovery
Background:
- Hypoxia critically influences hepatocellular carcinoma (HCC) progression and treatment resistance.
- Hypoxia-responsive microRNAs (HRMs) in canine HCC are not well understood.
- Investigating canine HCC offers insights into human disease mechanisms.
Purpose of the Study:
- Identify HRMs in canine HCC.
- Assess their diagnostic potential using circulating biomarkers.
- Evaluate translational relevance to human HCC.
Main Methods:
- Next-generation sequencing of canine HCC cell lines under normoxic and hypoxic conditions.
- RT-qPCR validation in hypoxic cells and clinical tissues.
- Analysis of plasma-derived extracellular vesicles (EVs) for miRNA detection.
- Cross-species comparison with human HCC datasets.
Main Results:
- Identified 11 HRMs, with consistent upregulation of cfa-miR-210 and cfa-miR-34a.
- cfa-miR-210 and cfa-miR-34a were significantly elevated in plasma EVs, showing high diagnostic accuracy (AUC 1.00 and 0.98).
- Pathway analysis revealed conserved signaling pathways related to hypoxia adaptation and stress response.
- Cross-species analysis indicated differing prognostic roles for miR-210 and miR-34a in canine versus human HCC.
Conclusions:
- Defined complementary HRM programs in canine HCC.
- HRMs, particularly cfa-miR-210 and cfa-miR-34a in EVs, are promising circulating biomarkers for HCC.
- Findings highlight conserved regulatory mechanisms with diagnostic and translational potential for human HCC.
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