Altered expression of collagen gene family members and its epigenetic background in equine Sarcoids

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Alterations in the genes involved in the creation of the extracellular matrix (ECM) were observed in our earlier transcriptome studies of sarcoids and their cell culture model. For a complete characterization of the underlying molecular pathways, it is imperative to comprehend the involvement of ECM modifications in the oncogenic transformation of sarcoid fibroblasts. Thus, the aim of this investigation was to describe the expression patterns of a set of genes that are essential for the rearrangements of the extracellular matrix, namely collagen genes, and elucidate possible mechanisms underlying the observed disruptions. To this end, we applied the RT-qPCR method on BPV-negative skin samples and sarcoid samples (n = 6 and 7; respectively) to perform relative quantification of the expression level of eight genes belonging to the collagen family and carried out an integrative analysis of the obtained data with previously characterized epigenetic signatures. The results showed aberrations in the level of chosen collagen genes in the sarcoids compared to the control, manifesting in their elevated levels in the tumor samples (p-value≤0.05). The upregulation of Col1A2, Col11A1, Col6A3, Col5A2, Col4A1, Col6A6, Col5A1, Col6A2 genes was detected in sarcoid samples. The identified changes were statistically significant (p-value≤0.05) and ranged from 1.43 (Col6A2) to 1.88 (Col6A3). Further investigation into the potential involvement of epigenetic mechanisms in the regulation of collagen gene levels in sarcoids revealed compelling evidence of DNA methylation and microRNAs playing significant roles. The findings suggest a complex interplay between gene expression, epigenetic regulation, and the dysregulation of the ECM in sarcoid pathogenesis.

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