Small extracellular vesicles orchestrated pathological communications between breast cancer cells and cardiomyocytes as a novel mechanism exacerbating anthracycline cardiotoxicity by fueling ferroptosis

作者：Dong Han, Tianhu Wang, Xiaoyao Li, Cheng Qin, Yingjie Zhang, Tingwen Zhou, Shan Gao, Weiwei Zhang, Yongjun Wang, Yan Ma, Feng Cao · 发表于：Redox Biology · 年份：2025 · DOI：10.1016/j.redox.2025.103843 · 被引用次数：35 · 研究领域：Extracellular vesicles in disease、Ferroptosis and cancer prognosis、MicroRNA in disease regulation

A) is revealed to mediate the upregulation of miR-338-3p in D-BCCs. D-BCCs-enriched miR-338-3p is packaged in sEVs and transferred into hiCMs in a RBMX-dependent manner, miR-338-3p further targets anti-ferroptotic genes CP, SLC7A11, and GPX4 to facilitate their degradation. Therapeutically, dual-functional decoying sEVs encapsulated with miR-338-3p inhibitor mitigate DOXIC in an orthotopic breast cancer mouse model. Clinically, plasma sEVs isolated from patients experiencing DOXIC enhance DOX-induced ferroptosis in hiCM, which is rescued by miR-338-3p inhibitor. Our findings uncovered for the first time that DOX-treated BCCs exacerbated DOXIC through releasing pro-ferroptotic miR-338-3p-enriched sEVs. Therefore, targeting sEVs-mediated tumor/cardiomyocyte pathological communication may offer a novel approach for the management of DOXIC.