Differences in miRNA differential expression in whole blood between horses with sarcoid regression and progression

Background Currently no methods are available to predict the clinical outcome of individual horses with equine sarcoid (ES) disease. Objective To investigate if whole blood microRNA (miRNA) profiles can predict the long-term development of ES tumors. Animals Five horses with regression and 5 with progression of ES lesions monitored over 5-7 years and 5 control horses free of ES for at least 5 years. Methods For this cohort study, RNA extracted from whole blood samples from the regression, progression, and control groups was used for high throughput sequencing. Known and novel miRNAs were identified using miRDeep2 and differential expression analysis was carried out by the DESeq2 algorithm. Target gene and pathway prediction as well as enrichment and network analyses were conducted using TarBase, mirPath, and metaCore from GeneGo. Results Fourteen miRNAs were differentially expressed between regression and progression groups after accounting for the control condition: 4 miRNAs (28.6%) were upregulated and 10 miRNAs (71.4%) were downregulated with >2-fold change. Seven of the 10 downregulated miRNAs are encoded in an miRNA cluster on equine chromosome 24, homologous to the well-known 14q32 cluster in humans. Their target genes show enrichment for pathways involved in viral carcinogenesis. Conclusions and Clinical Importance Whole blood miRNA expression profiles are associated with long-term ES growth in horses and warrant further validation as prognostic biomarkers in a larger study cohort. Deregulation of miRNAs on equine chromosome 24 might represent a trigger for ES development.