miRNA-mRNA integrative profiling in canine tubulopapillary mammary carcinoma.

Abstract

Canine mammary tumors (CMTs) are the most common neoplasia in intact female dogs. There are different histological subtypes, which are related to tumor behavior and prognosis. Among them, we highlight the tubulopapillary subtype, one of the most prevalent subtypes in female dogs. Although not the most aggressive subtype overall, it is associated with significantly higher lethality compared to other common subtypes, suggesting an underlying dysregulation of gene expression. However, global expression of RNAs in tubulopapillary CMTs is not available in the literature. Here, we analyzed the differential expression of mRNAs and miRNAs of tubulopapillary CMTs (n = 4) and compared them with normal mammary tissues (n = 4) using microarray. We found 842 downregulated and 385 upregulated mRNAs in the CMTs, which corresponded to the enrichment of 10 biological pathways. Also, we found 30 upregulated miRNAs and one downregulated (cfa-miR-345) in CMTs. Among the differentially expressed mRNAs, we identified 360 mRNAs that were targets of the differentially expressed miRNAs, which enriched 23 biological pathways, with the "Endocytosis" pathway being of particular significance. These findings highlight the complex interactions between mRNAs and miRNAs in tubulopapillary CMTs, thereby improving the understanding of the pathophysiology of this CMT subtype and providing targets for functional validation of biomarkers and/or therapeutics.