Aberrant O-glycosylation genes and miR-21-5p targets define a molecular signature of tumor aggressiveness in triple-negative breast cancer

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ID: 318692
2026
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Abstract
Abstract Aberrant O-glycosylation and miRNA dysregulation are established features of tumor aggressiveness, particularly in triple-negative breast cancer (TNBC). Using a Cosmc-silenced 4 T1 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–mesenchymal transition and immune modulation. Integrative single-cell RNA sequencing (scRNA-seq) of the 4 T1 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—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 = 0.015). 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.
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Authors Alexis Germán Murillo Carrasco, Mercedes Landeira, Tatiane Katsue Furuya, Maria José Ferreira Alves, Maitê Lôbo Kolarik, Leandro M. Colli, Patrícia P. Reis, Roger Chammas, Teresa Freire
Journal glycobiology
Year 2026
DOI
10.1093/glycob/cwag046
URL
https://doi.org/10.1093/glycob/cwag046
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