Differentially expressed microRNAs, including a large microRNA cluster on chromosome 24, are associated with equine sarcoid and squamous cell carcinoma.
Abstract: The aim of this study was to investigate microRNA (miRNA) differential expression in the two most common equine skin tumours, equine sarcoid (ES) and squamous cell carcinoma (SCC), and its potential influence on the tumour microenvironment at post-transcriptional level. We investigated miRNA fingerprints in four subgroups: mild (ESM) and aggressive (ESA) ES and ocular SCC (oSCC) and genital SCC (gSCC). Three tumours and three control samples were included in each of the four subgroups. Following next generation sequencing, miRNA differential expression analysis using DESeq2 was carried out. Pathways associated with the human mature homologues of identified dysregulated miRNAs were predicted using DIANA- miRPath v3.0. When comparing tumour vs control tissue, 57 miRNAs in ESM, six in ESA, 47 in oSCC and zero in gSCC were found to be differentially expressed and may thus serve as potential diagnostic tissue biomarkers. Whereas, ES lesions in general were associated with downregulation of the miR-200 family, which may trigger epithelial-mesenchymal transition, ESM lesions were associated with upregulation of the proposed tumour-suppressive miRNA cluster on equine chromosome 24. In contrast, the oSCC tumours showed downregulation of this cluster as well as downregulation of the miR-34 family, which may favour oSCC tumour cell metabolism. To further validate the proposed diagnostic miRNA fingerprints and their suggested biological effects, further miRNA studies need to be carried out in larger study cohorts.
© 2019 John Wiley & Sons Ltd.
Publication Date: 2019-02-15 PubMed ID: 30684296DOI: 10.1111/vco.12458Google Scholar: Lookup
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- Comparative Study
- Journal Article
Summary
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This study explored how microRNA (miRNA) expression varies in the two most prevalent types of skin tumors in horses, equine sarcoid and squamous cell carcinoma, and how this could influence tumor development. Significant differences were found in miRNA expression between various different classes of these tumors and controls, suggesting potential use in diagnosis.
Objective and Methods
- This study’s goal was to analyze variations in miRNA expression in the two most common horse skin tumors, equine sarcoid (ES) and squamous cell carcinoma (SCC). The research also aimed to understand the potential impact of these variations on the tumor microenvironment. The tumors were divided into four groups for the study: mild equine sarcoid (ESM), aggressive equine sarcoid (ESA), ocular SCC (oSCC), and genital SCC (gSCC).
- Each subclass included three tumor samples and three control samples. Next-generation sequencing was employed to examine the miRNA profiles in these samples, followed by differential expression analysis using DESeq2. The pathways that the human matches of the identified dysregulated miRNAs could participate in were predicted using the DIANA-miRPath software program.
Findings
- The analysis revealed various miRNAs that were differentially expressed between tumor and control tissues for each of the four groups. A total of 57 miRNAs in ESM, six in ESA, 47 in oSCC, and none in gSCC were identified as differentially expressed, suggesting their possible role as tissue biomarkers for diagnosis.
- In terms of specific findings, ES lesions were generally associated with a reduced expression of the miR-200 family, which might trigger epithelial-mesenchymal transition, a process linked to tumor development and metastasis.
- In contrast, ESM lesions showed increased activity of a miRNA cluster on equine chromosome 24, which has been proposed to have tumor-suppressive properties.
- Notably, in oSCC tumors, this cluster was depressed, as was the miR-34 family, which may thus promote the metabolism of oSCC tumor cells.
Implications and Future Research
- This study suggests that miRNA fingerprints could serve as potential diagnostic tools for horse skin tumors. However, the biological effects of these miRNA fingerprints and their effectiveness as diagnostic tools need further validation.
- Future investigations should be performed on larger cohorts to affirm these findings and to delve deeper into the role of these microRNAs in the development and progression of equine skin tumors.
Cite This Article
APA
Bogedale K, Jagannathan V, Gerber V, Unger L.
(2019).
Differentially expressed microRNAs, including a large microRNA cluster on chromosome 24, are associated with equine sarcoid and squamous cell carcinoma.
Vet Comp Oncol, 17(2), 155-164.
https://doi.org/10.1111/vco.12458 Publication
Researcher Affiliations
- Department of Clinical Veterinary Medicine, Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Bern, Switzerland.
- Department of Clinical Research and Veterinary Public Health, Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
- Department of Clinical Veterinary Medicine, Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Bern, Switzerland.
- Department of Clinical Veterinary Medicine, Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Bern, Switzerland.
MeSH Terms
- Animals
- Biomarkers, Tumor / genetics
- Carcinoma, Squamous Cell / genetics
- Carcinoma, Squamous Cell / pathology
- Carcinoma, Squamous Cell / veterinary
- Chromosome Mapping / veterinary
- Chromosomes
- Eye Neoplasms / genetics
- Eye Neoplasms / pathology
- Eye Neoplasms / veterinary
- Female
- Gene Expression Regulation, Neoplastic
- Horse Diseases / genetics
- Horse Diseases / pathology
- Horses
- Male
- MicroRNAs / genetics
- Mouth Neoplasms / genetics
- Mouth Neoplasms / pathology
- Mouth Neoplasms / veterinary
- Sarcoidosis / genetics
- Sarcoidosis / pathology
- Sarcoidosis / veterinary
- Skin Neoplasms / genetics
- Skin Neoplasms / pathology
- Skin Neoplasms / veterinary
Grant Funding
- Swiss Institute of Equine Medicine Research funds
Citations
This article has been cited 9 times.- Hamza E, Cosandey J, Gerber V, Koch C, Unger L. The potential of three whole blood microRNAs to predict outcome and monitor treatment response in sarcoid-bearing equids. Vet Res Commun 2023 Jan;47(1):87-98.
- Cosandey J, Hamza E, Gerber V, Ramseyer A, Leeb T, Jagannathan V, Blaszczyk K, Unger L. Diagnostic and prognostic potential of eight whole blood microRNAs for equine sarcoid disease. PLoS One 2021;16(12):e0261076.
- Jindra C, Hainisch EK, Rümmele A, Wolschek M, Muster T, Brandt S. Influenza virus vector iNS1 expressing bovine papillomavirus 1 (BPV1) antigens efficiently induces tumour regression in equine sarcoid patients. PLoS One 2021;16(11):e0260155.
- Zarski LM, Giessler KS, Jacob SI, Weber PSD, McCauley AG, Lee Y, Soboll Hussey G. Identification of Host Factors Associated with the Development of Equine Herpesvirus Myeloencephalopathy by Transcriptomic Analysis of Peripheral Blood Mononuclear Cells from Horses. Viruses 2021 Feb 24;13(3).
- Unger L, Abril C, Gerber V, Jagannathan V, Koch C, Hamza E. Diagnostic potential of three serum microRNAs as biomarkers for equine sarcoid disease in horses and donkeys. J Vet Intern Med 2021 Jan;35(1):610-619.
- Crausaz M, Launois T, Smith-Fleming K, McCoy AM, Knickelbein KE, Bellone RR. DDB2 Genetic Risk Factor for Ocular Squamous Cell Carcinoma Identified in Three Additional Horse Breeds. Genes (Basel) 2020 Dec 5;11(12).
- Cao J, Sun L, An J, Zhang H, He X, Shen H. [MicroRNA-200c-3p inhibits proliferation of nephroblastoma cells by targeting CCNE2]. Nan Fang Yi Ke Da Xue Xue Bao 2020 Sep 30;40(9):1246-1252.
- Zheng JF, Guo NH, Zi FM, Cheng J. Long Noncoding RNA H19 Promotes Tumorigenesis of Multiple Myeloma by Activating BRD4 Signaling by Targeting MicroRNA 152-3p. Mol Cell Biol 2020 Jan 16;40(3).
- Beermann A, Hamza E, Reinhard S, Koch C, Oberhänsli T, Unger L. Selected microRNAs as biomarkers in sarcoid-affected horses under immunotherapy with a mistletoe extract. J Vet Diagn Invest 2026 Jan;38(1):33-40.
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