Abstract
BACKGROUND: Triple-negative breast cancer (TNBC) is a notoriously aggressive subtype with poor prognosis. MicroRNAs (miRNAs) critically regulate epithelial-mesenchymal transition (EMT), a central driver of cancer metastasis. Nevertheless, the function of hsa-miR-5100 in TNBC was poorly understood. This study investigated the effects of miR-5100 on the malignant behaviors of TNBC cells, its correlation with patient prognosis, and underlying molecular mechanisms. METHODS: Plasma levels of miR-5100 were assessed in a cohort of 80 TNBC patients and 80 healthy controls. Based on miR-5100 expression levels, patients were categorized into high and low groups, with 5-year survival as the primary endpoint for Kaplan-Meier and Cox regression analyses. MiR-5100 was assessed for its effects on proliferation, migration, invasion, and EMT in TNBC cell lines (MDA-MB-231 and MDA-MB-468), with its direct interaction with SMAD4 confirmed by dual-luciferase reporter assay. RESULTS: Upregulation of miR-5100 was observed in TNBC patients. Elevated miR-5100 levels correlated with advanced TNM stage, lymph node metastasis, high Ki-67 proliferation index, and reduced survival. Overexpression of miR-5100 promoted the proliferation, migration and invasion of TNBC cells. MiR-5100 overexpression mediated the reciprocal regulation of E-cadherin (down) and N-cadherin (up) at both mRNA and protein levels in TNBC cells. Mechanistically, the oncogenic effects of miR-5100 on TNBC cell proliferation, migration, invasion, and EMT were mediated through its direct targeting of SMAD4. CONCLUSIONS: MiR-5100 was upregulated in TNBC patients and was associated with a poor prognosis. By targeting SMAD4, miR-5100 promoted the malignant phenotypes of TNBC cells in vitro, suggesting its potential research value as a prognostic biomarker and therapeutic target. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12957-026-04271-0.