Background Osteosarcoma (OS) is the most common primary malignant bone tumour in dogs and human beings, characterised by similar genetic and clinical features. With the aim to define similarities and differences in the biological aspects involved in OS progression, a comparative study was performed to create a model to improve patient outcome.
Methods First, the expression of microRNAs (miRNAs) belonging to the cluster miR-106b-25 (miR-106b, miR-25 and miR-93-5p) in human and canine OS tissue was compared.
Results miR-25 and miR-106b presented a variable expression not significantly different from the corresponding normal bone, while miR-93-5p expression was increased in all OS specimens, with higher levels in the canine subset compared with human. Accordingly, its target p21 presented a weaker and less homogeneous immunostaining distribution in the canine group. Given the high expression of miR-93-5p in all OS specimens, the functional response of human 143B and canine DAN OS cells to miRNA inhibition was evaluated. Although p21 expression increased after miR-93-5p inhibition both at mRNA and protein level, a more significant cell response in terms of proliferation and apoptosis was seen in canine OS cells.
Conclusions In conclusion, canine OS tissue and cell line presented higher expression levels of miR-93-5p than human OS. In addition, the introduction of miR-93-5p inhibitor caused a cell response in 143B and DAN that differed for the more intense functional impact in the canine OS cell line.
- miRNA expression
- p21 target gene
- protein expression
- osteosarcoma cell lines
- miR-93-5p inhibition
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Funding This work was supported by 5x1000 contribution to the Rizzoli Orthopaedic Institute and by 'Fondazione Cassa di Risparmio di Perugia' project, "Canine and human osteosarcoma biological models’ studies in comparative oncology. From microRNA to the cellular and biomolecular signals control". Code 2016.0182.021.
Ethics approval The study was approved by the Rizzoli Institute Ethic Committee (human OS population no. 0033276).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article.
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