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Updated: Jul 9, 2026
Cancer-Associated Fibroblasts from Mouse Mammary Tumors as Tools for Molecular and Computational Studies
Published on: July 3, 2025
Biphasic tissue expression of cfa-miR-409-3p and cfa-miR-4270 during malignant transformation in canine mammary
Luíz Guilherme Dércore Benevenuto1, Zara Alves Lacerda1, Reiner Silveira de Moraes2
1Department of Veterinary Surgery and Anesthesiology, Faculty of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Botucatu, Brazil.
Introduction:
Canine mammary tumors (CMTs) are the most common malignancy in intact female dogs and represent a well-established spontaneous model for human breast cancer. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression critically involved in carcinogenesis and are candidate non-invasive biomarkers for tumor diagnosis and prognosis.
Methods:
This exploratory study evaluated the tissue and plasma expression of five candidate miRNAs-cfa-miR-133a, cfa-miR-127-3p, cfa-miR-652, cfa-miR-409-3p, and cfa-miR-4270-in two independent cohorts. The tissue cohort comprised 57 mammary samples (33 carcinomas, 14 adenomas, and 10 normal tissues) analyzed by poly(A) tailing-based SYBR Green RT-qPCR. The plasma cohort included 75 dogs with mammary carcinomas and 5 healthy controls, quantified by TaqMan Advanced miRNA Assays.
Results:
Tissue analysis revealed that cfa-miR-133a was significantly downregulated in both adenomas and carcinomas relative to normal tissue (p < 0.001), consistent with early and sustained tumor suppressor loss during mammary carcinogenesis. Notably, cfa-miR-409-3p and cfa-miR-4270 displayed a biphasic expression pattern: significantly downregulated in adenomas relative to normal tissue and partially restored in carcinomas-a biphasic pattern that was statistically significant for cfa-miR-4270 (p = 0.008) and showed a consistent trend for cfa-miR-409-3p (p = 0.054)-suggesting context-dependent regulation during the adenoma-to-carcinoma transition. In plasma, no statistically significant differences were detected across all clinical comparisons, including carcinoma vs. healthy controls, metastatic vs. non-metastatic disease, tumor stage, reproductive status, and survival outcomes.
Discussion:
These findings indicate that tissue-level miRNA dysregulation in CMTs follows biologically coherent, progression-associated patterns aligned with the roles of human orthologs in breast cancer, whereas no significant circulating signatures were detected in plasma; however, the plasma analyses were limited by a small control group and were underpowered, and these negative findings should not be interpreted as evidence against biological relevance. These results support the design of larger, prospectively standardized investigations to validate tissue miRNA biomarkers and advance liquid biopsy approaches in canine mammary oncology.
