# Divergent Tissue and Circulatory Expression of miR-10a in Canine Hepatocellular Carcinoma: Comparative Insights from Human HCC

## TL;DR

This study identifies miR-10a as a potential non-invasive biomarker for canine liver cancer, with insights relevant to human liver cancer due to shared molecular pathways.

## Contribution

The study reveals a conserved role of miR-10a in canine and human HCC, highlighting its diagnostic potential and conserved molecular mechanisms.

## Key findings

- cfa-miR-10a is significantly downregulated in canine HCC tissues but enriched in plasma exosomes, showing strong diagnostic performance.
- The mature sequence of cfa-miR-10a is highly conserved with hsa-miR-10a-5p, which is also downregulated in human HCC tissues.
- Conserved Proteoglycans in cancer pathways, mediated by ACTG1, SDC1, FRS2, and WNT9B, are linked to miR-10a in both species.

## Abstract

Canine hepatocellular carcinoma (HCC), the most common primary liver malignancy in dogs, shares many clinicopathological and molecular similarities with human HCC. However, its molecular characteristics remain insufficiently defined, and reliable diagnostic biomarkers are lacking. Elucidating dysregulated microRNAs (miRNAs) may aid in both disease characterization and comparative oncology research. Small RNA sequencing datasets from canine HCC were analyzed to identify significantly dysregulated miRNAs with high expression and biomarker potential. The top candidate was validated in clinical tissues, cell lines, patient’s plasma and plasma exosomes using RT-qPCR. Comparative analyses were conducted using human HCC datasets (TCGA and GEO), followed by target prediction and functional enrichment to identify conserved molecular pathways. Among the 59 differentially expressed miRNAs, cfa-miR-10a showed the highest average expression level and yet was significantly downregulated in canine HCC tissues. RT-qPCR confirmed reduced expression of cfa-miR-10a in canine HCC tissues, whereas plasma exosomes showed significant enrichment, demonstrating excellent diagnostic performance (AUC = 0.94). The mature sequence of cfa-miR-10a is highly conserved with hsa-miR-10a-5p. TCGA datasets confirmed downregulation of hsa-miR-10a-5p in HCC tissues, whereas a GEO dataset showed no significant change in serum exosome levels. Target prediction and functional annotation identified 59 overlapping genes, with the Proteoglycans in cancer pathways being conserved in both species, mediated by ACTG1, SDC1, FRS2, and WNT9B. Collectively, these findings demonstrate distinct intra-tumoral and exosomal expression pattern of miR-10a in canine HCC and support its potential as a non-invasive biomarker with translational relevance.