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Using a Cosmc-silenced 4T1 murine model (Tn+), characterized by truncated O-glycans and enhanced metastatic potential, tissue and serum miRNA profiling identified miR-21-5p as a circulating marker associated with the Tn+ phenotype. Transcriptomic analysis revealed that miR-21-5p targets multiple tumor suppressor genes, including Btg2, Spry1, Tbx2, Rhob, and Dusp8, suggesting its involvement in epithelial\u2013mesenchymal transition and immune modulation. Integrative single-cell RNA sequencing (scRNA-seq) of the 4T1 tumor microenvironment revealed distinct cellular clusters with inverse expression patterns of GALNT enzymes (involved in Tn synthesis) and miR-21-5p target genes, defining Tn+-like and Tn\u2212-like subpopulations. Translating these findings to human breast cancer (TCGA-BRCA), a prognostic model combining clinical variables (age, metastasis, PAM50 subtype) with three-gene expression (OLR1, PCSK6, and GALNT6) significantly improved patient risk stratification (P\u00a0=\u00a00.015). By integrating multi-omics analyses (scRNA-seq, TCGA) with an aggressive Tn+ TNBC model, this study defines a novel three-gene prognostic signature that links the glyco-miRNA axis to tumor aggressiveness, offering a promising tool for advanced patient stratification and the development of precision glyco-therapeutics.<\/jats:p>","DOI":"10.1093\/glycob\/cwag046","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T11:53:02Z","timestamp":1782388382000},"source":"Crossref","is-referenced-by-count":0,"title":["Aberrant O-glycosylation genes and miR-21-5p targets define a molecular signature of tumor aggressiveness in triple-negative breast cancer"],"prefix":"10.1093","volume":"36","author":[{"given":"Alexis Germ\u00e1n","family":"Murillo Carrasco","sequence":"first","affiliation":[{"name":"Center for Translational Research in Oncology (LIM24), Instituto do Cancer do Estado de Sao Paulo (ICESP), Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP) , S\u00e3o Paulo 01246-000 , Sao Paulo,","place":["Brazil"]},{"name":"Comprehensive Center for Precision Oncology, Universidade de S\u00e3o Paulo , S\u00e3o Paulo 01246-000 , Sao Paulo,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Landeira","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunomodulaci\u00f3n y Vacunas, Unidad Acad\u00e9mica de Inmunobiolog\u00eda, Facultad de Medicina, Universidad de la Rep\u00fablica , General Flores 2125, 11800 Montevideo ,","place":["Uruguay"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiane Katsue","family":"Furuya","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Oncology (LIM24), Instituto do Cancer do Estado de Sao Paulo (ICESP), Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP) , S\u00e3o Paulo 01246-000 , Sao Paulo,","place":["Brazil"]},{"name":"Comprehensive Center for Precision Oncology, Universidade de S\u00e3o Paulo , S\u00e3o Paulo 01246-000 , Sao Paulo,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Jos\u00e9","family":"Ferreira Alves","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Oncology (LIM24), Instituto do Cancer do Estado de Sao Paulo (ICESP), Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP) , S\u00e3o Paulo 01246-000 , Sao Paulo,","place":["Brazil"]},{"name":"Comprehensive Center for Precision Oncology, Universidade de S\u00e3o Paulo , S\u00e3o Paulo 01246-000 , Sao Paulo,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mait\u00ea","family":"Lobo Kolarik","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Oncology, Department of Medical Imaging, Hematology and Clinical Oncology, Faculty of Medicine of Ribeir\u00e3o Preto, University of S\u00e3o Paulo (USP) , Av. 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