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ARTICLE

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

Tingting Yang1, Meng Guan1, Xin Guan1, Lihua Kang1, Xiaomeng Wang1, Yanjie Guan1, Yang Yang2, Wei Deng3, Guoxiang Wang1,*
1 Cancer Center, First Hospital of Jilin University, Jilin University, Changchun, China
2 Department of Hematology and Oncology, China-Japan Union Hospital of Jilin University, Jilin University, Changchun, China
3 Engineering Research Center for Digital Medicine and Health of Guangxi Higher Education Institutions, Guangxi Medical University, Nanning, China
* Corresponding Author: Guoxiang Wang. Email: email
(This article belongs to the Special Issue: Novel Biomarkers and Treatment Strategies in Solid Tumor Diagnosis, Progression, and Prognosis (Ⅱ))

Oncology Research https://doi.org/10.32604/or.2026.083563

Received 06 April 2026; Accepted 04 June 2026; Published online 24 June 2026

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.

Keywords

Breast cancer; exosomes; miR-92b-3p; angiogenesis; vascular permeability

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