Abstract

Background: Tumor-driven vascular remodeling is crucial for breast cancer metastasis; yet, the role of tumor-derived exosomal miRNAs in this process remains underexplored. This study aimed to investigate the clinical relevance and the underlying mechanism of breast cancer-derived exosomal miR-92b-3p in endothelial reprogramming. Methods: miR-92b-3p expression was evaluated in the TCGA cohort and clinical patient samples. The effects of exosomal miR-92b-3p from breast cancer cells on recipient human microvascular endothelial cells (HMVECs) were assessed using in vitro angiogenesis, migration, and permeability assays, alongside in vivo murine xenograft models. Mechanistic targets were validated via dual-luciferase and rescue experiments. Results: miR-92b-3p was significantly upregulated in breast cancer tissues and plasma exosomes, correlating with advanced stages, poor survival, and exhibiting high diagnostic accuracy. Breast cancer-derived exosomes effectively transferred miR-92b-3p into HMVECs, significantly promoting angiogenesis, endothelial migration, and transendothelial permeability. In vivo , overexpression of miR-92b-3p accelerated tumor growth, vascularization, and circulating tumor cell (CTC) dissemination. Mechanistically, exosomal miR-92b-3p directly targeted and suppressed PTEN in endothelial cells; moreover, restoring PTEN expression fully abrogated the exosome-induced pro-angiogenic and hyperpermeable phenotypes. Conclusions: Breast cancer-derived exosomal miR-92b-3p disrupts the vascular barrier and promotes tumor angiogenesis by targeting endothelial PTEN, thereby facilitating metastasis. Circulating exosomal miR-92b-3p represents a promising candidate liquid-biopsy biomarker for breast cancer progression.