{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:16:32Z","timestamp":1791825392423,"version":"4.3.4"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This exploratory study evaluated the tissue and plasma expression of five candidate miRNAs\u2014cfa-miR-133a, cfa-miR-127-3p, cfa-miR-652, cfa-miR-409-3p, and cfa-miR-4270\u2014in 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Tissue analysis revealed that cfa-miR-133a was significantly downregulated in both adenomas and carcinomas relative to normal tissue (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001), 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\u2014a biphasic pattern that was statistically significant for cfa-miR-4270 (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.008) and showed a consistent trend for cfa-miR-409-3p (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.054)\u2014suggesting 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fvets.2026.1861662","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T09:56:16Z","timestamp":1782208576000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Biphasic tissue expression of cfa-miR-409-3p and cfa-miR-4270 during malignant transformation in canine mammary tumors: an exploratory study"],"prefix":"10.3389","volume":"13","author":[{"given":"Lu\u00edz Guilherme D\u00e9rcore","family":"Benevenuto","sequence":"first","affiliation":[{"name":"Department of Veterinary Surgery and Anesthesiology, Faculty of Veterinary Medicine and Animal Science, S\u00e3o Paulo State University (UNESP)","place":["Botucatu, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zara Alves","family":"Lacerda","sequence":"additional","affiliation":[{"name":"Department of Veterinary Surgery and Anesthesiology, Faculty of Veterinary Medicine and Animal Science, S\u00e3o Paulo State University (UNESP)","place":["Botucatu, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reiner Silveira","family":"de Moraes","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinics, Faculty of Veterinary Medicine and Animal Science, S\u00e3o Paulo State University (UNESP)","place":["Botucatu, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia de Faria","family":"Lainetti","sequence":"additional","affiliation":[{"name":"Department of Veterinary Surgery and Anesthesiology, Faculty of Veterinary Medicine and Animal Science, S\u00e3o Paulo State University (UNESP)","place":["Botucatu, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Giulia Gabriel","family":"da Rocha Cesario","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinics, Faculty of Veterinary Medicine and Animal Science, S\u00e3o Paulo State University (UNESP)","place":["Botucatu, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre Matheus Baesso","family":"Cavalca","sequence":"additional","affiliation":[{"name":"Department of Veterinary Surgery and Anesthesiology, Faculty of Veterinary Medicine and Animal Science, S\u00e3o Paulo State University (UNESP)","place":["Botucatu, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee Laufer","family":"Amorim","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinics, Faculty of Veterinary Medicine and Animal Science, S\u00e3o Paulo State University (UNESP)","place":["Botucatu, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Eduardo","family":"Fonseca-Alves","sequence":"additional","affiliation":[{"name":"Department of Veterinary Surgery and Anesthesiology, Faculty of Veterinary Medicine and Animal Science, S\u00e3o Paulo State University (UNESP)","place":["Botucatu, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1186\/s12885-017-3751-1","article-title":"MicroRNA expression patterns in canine mammary cancer show significant differences between metastatic and non-metastatic cancers","volume":"14","author":"Bulkowska","year":"2017","journal-title":"Oncol Lett"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1631\/jzus.B1400184","article-title":"MicroRNAs in breast cancer: oncogene and tumor suppressors with clinical 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