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Integrated transcriptomic profiling reveals oncogenic pathways and chimeric transcripts in equine sarcoid lesions with predominant BPV1 detection.
Abstract: Sarcoids are the most common cutaneous tumors in horses, representing up to 90% (35%-90%) of skin neoplasms. Mostly caused by Bovine Papillomavirus (BPVs) infections, sarcoids are highly resistant to therapy and prone to recurring, posing a significant threat to equine health. The aim of this study is to explore molecular pathogenetic mechanisms underlying the development of equine sarcoids, by applying transcriptomic approach. After testing samples for viral DNA, both mRNA and small RNA expression was analyzed via high-throughput Illumina sequencing comparing 12 sarcoids and 12 healthy skin samples as controls. Differentially expressed genes (DEGs), DE miRNAs (sarcoids vs. controls) and miRNA-DEG couples with opposite expression trends, were retrieved and subjected to a functional analysis. Over 6K DEGs emerged, 3620 down-regulated and 2415 up-regulated along with 145 DE miRNAs, 56 downregulated and 89 upregulated. Among the enriched biological processes for DEGs, some were related to growth factors production and collagen binding, cell migration and proliferation, tissue morphogenesis and inflammatory response. Interestingly, "Pathways in cancer" and "Hippo signaling pathway" were enriched KEGG pathways for the miRNA-DEG couples. Our data identified a great transcription discrepancy between sarcoid lesions and healthy skin with an overall enrichment for processes related to cellular transformation. RNA-seq sequencing depth allowed the search for candidate chimeric transcripts associated with viral integration events. Chimeric RNAs can influence gene regulation and may contribute to tumor growth and immune modulation. Via computational analysis we identified six fusion loci in tumor samples and in two sarcoid margins, with the most frequent event involving WNT10B and FKBP11. This fusion, detected in 6/10 sarcoids, is of particular interest since WNT10B activates the WNT/β-catenin cascade, while FKBP11 has been implicated in osteosarcoma progression. Although functional validation is ongoing, this represents the first report of chimeric transcripts in equine sarcoids, opening new perspectives on BPV-driven oncogenesis.
Copyright © 2026 Mecocci, Capomaccio, Porcellato, Dell’Anno, Ratto, Mechelli, De Paolis, Fruscione, Passeri, Gialletti, Pepe, Ghelardi, Razzuoli and Cappelli.
Publication Date: 2026-06-19 PubMed ID: 42404695PubMed Central: PMC13328017DOI: 10.3389/fmolb.2026.1818241Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
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Overview
- This study investigates the molecular mechanisms behind equine sarcoids, common skin tumors in horses primarily caused by Bovine Papillomavirus type 1 (BPV1), using transcriptomic profiling to identify changes in gene and microRNA expression and potential viral integration events contributing to cancer development.
Background
- Equine Sarcoids: The most frequent skin tumors in horses, accounting for up to 90% of skin neoplasms.
- Cause: Primarily associated with infection by Bovine Papillomaviruses, especially BPV1.
- Clinical Challenge: Sarcoids are difficult to treat, resistant to therapies, and prone to recurrence, posing a major health issue in equine populations.
Objective
- To explore the molecular and pathogenetic mechanisms involved in the development of equine sarcoids, focusing on gene expression changes and the presence of chimeric (fusion) transcripts due to viral integration, by applying a transcriptomic approach.
Methods
- Sample Collection: 12 equine sarcoid tumor samples and 12 healthy skin samples were collected.
- Viral DNA Testing: Samples were tested for BPV DNA to confirm viral presence.
- Sequencing: High-throughput Illumina sequencing was performed to analyze both messenger RNA (mRNA) and small RNA (including microRNAs) expression profiles.
- Analysis: Differential expression analysis compared sarcoids versus healthy controls to identify differentially expressed genes (DEGs) and microRNAs (DE miRNAs).
- Functional Enrichment: Biological processes and pathways enriched among DEGs and miRNA-DEG pairs (with opposite expression) were identified, focusing on cancer-related pathways.
- Chimeric Transcript Search: Deep RNA sequencing data was computationally analyzed to detect fusion transcripts potentially arising from viral integration events.
Key Results
- Differentially Expressed Genes: More than 6,000 DEGs were identified — 3,620 genes were downregulated and 2,415 were upregulated in sarcoids compared to controls.
- Differentially Expressed microRNAs: 145 DE miRNAs were found, with 56 downregulated and 89 upregulated in tumor samples.
- Biological Processes Enriched: DEGs were enriched in processes such as:
- Growth factor production
- Collagen binding
- Cell migration and proliferation
- Tissue morphogenesis
- Inflammatory response
- KEGG Pathways: Notably enriched pathways included “Pathways in cancer” and the “Hippo signaling pathway,” both involved in cell growth regulation and oncogenesis.
Significance of Transcriptional Findings
- The study demonstrated significant transcriptional differences in sarcoid lesions versus normal skin, highlighting molecular changes consistent with cellular transformation and tumor progression.
- The identified miRNA-DEG interactions suggest complex regulatory networks influencing tumor biology.
Discovery of Chimeric Transcripts
- Using deep RNA-seq, six fusion loci were identified in tumor samples, and two in sarcoid margins, representing potential sites of viral integration.
- Most Frequent Fusion: A chimeric transcript involving genes WNT10B and FKBP11 was detected in 6 out of 10 tumors analyzed.
- Biological Relevance:
- WNT10B is important because it activates the WNT/β-catenin signaling pathway, which is critical for regulating cell proliferation and differentiation and frequently implicated in cancer.
- FKBP11 has been linked to tumor progression in osteosarcoma, suggesting a role in oncogenic processes.
- This discovery is the first report of chimeric transcripts in equine sarcoids, potentially implicating new mechanisms of BPV-driven tumorigenesis.
Impact and Future Directions
- The identified gene expression changes and discovery of fusion transcripts open new avenues to understand how BPV infection promotes sarcoid tumor development.
- Chimeric RNAs may alter gene regulation, contribute to tumor growth, and affect immune responses within the tumor microenvironment.
- Ongoing functional validation is necessary to confirm the biological roles of these fusion transcripts.
- This research enhances understanding of viral oncogenesis in horses and may guide future diagnostic or therapeutic strategies targeting molecular pathways and viral integration events.
Cite This Article
APA
Mecocci S, Capomaccio S, Porcellato I, Dell'Anno F, Ratto R, Mechelli L, De Paolis L, Fruscione F, Passeri B, Gialletti R, Pepe M, Ghelardi A, Razzuoli E, Cappelli K.
(2026).
Integrated transcriptomic profiling reveals oncogenic pathways and chimeric transcripts in equine sarcoid lesions with predominant BPV1 detection.
Front Mol Biosci, 13, 1818241.
https://doi.org/10.3389/fmolb.2026.1818241 Publication
Researcher Affiliations
- Department of Veterinary Medicine, University of Perugia, Perugia, Italy.
- Sports Horse Research Center (CRCS), University of Perugia, Perugia, Italy.
- Department of Veterinary Medicine, University of Perugia, Perugia, Italy.
- Sports Horse Research Center (CRCS), University of Perugia, Perugia, Italy.
- Department of Veterinary Medicine, University of Perugia, Perugia, Italy.
- Sports Horse Research Center (CRCS), University of Perugia, Perugia, Italy.
- Department of Veterinary Medicine, University of Perugia, Perugia, Italy.
- National Reference Center of Veterinary and Comparative Oncology (CEROVEC), Genoa, Italy.
- Department of Veterinary Medicine, University of Perugia, Perugia, Italy.
- Sports Horse Research Center (CRCS), University of Perugia, Perugia, Italy.
- Department of Veterinary Medicine, University of Perugia, Perugia, Italy.
- Sports Horse Research Center (CRCS), University of Perugia, Perugia, Italy.
- National Reference Center of Veterinary and Comparative Oncology (CEROVEC), Genoa, Italy.
- National Reference Center of Veterinary and Comparative Oncology (CEROVEC), Genoa, Italy.
- Department of Veterinary Medicine, University of Parma, Parma, Italy.
- Department of Veterinary Medicine, University of Parma, Parma, Italy.
- Department of Veterinary Medicine, University of Perugia, Perugia, Italy.
- Sports Horse Research Center (CRCS), University of Perugia, Perugia, Italy.
- UOC Ostetricia e Ginecologia, Azienda Usl Toscana Nord-Ovest, Massa, Italy.
- National Reference Center of Veterinary and Comparative Oncology (CEROVEC), Genoa, Italy.
- Department of Veterinary Medicine, University of Perugia, Perugia, Italy.
- Sports Horse Research Center (CRCS), University of Perugia, Perugia, Italy.
Conflict of Interest Statement
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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