Breast Cancer Cell-Derived Exosomal miR-92b-3p Promotes Tumor Angiogenesis and Metastasis by Suppressing PTEN in Vascular Endothelial CellsOA

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 expressionwas evaluated in the TCGAcohort 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.