Exosomal miR-3529-3p increases the sensitivity of trastuzumab via Wnt/β-catenin signaling pathway by targeting HOOK3

Trastuzumab is frequently utilized to treat human epidermal growth factor receptor 2 (HER2)-positive breast Cancer, though its effectiveness is frequently hindered by the development of chemotherapy resistance. Recent research has indicated that exosomes, serving as carriers for genetic material exchanged among diverse tumor cell populations, contribute to the transmission of drug resistance, thereby promoting Cancer progression. However, the exact mechanisms through which exosomes originating from breast Cancer influence drug resistance remain unclear. In this study, we performed Sequencing on exosomes both before and after trastuzumab treatment. Our results demonstrated a significant reduction in miR-3529-3p levels in exosomes from breast Cancer patients following trastuzumab treatment compared to pre-treatment levels. Furthermore, miR-3529-3p was also downregulated in cells resistant to trastuzumab. Notably, overexpressing miR-3529-3p counteracted trastuzumab resistance. Additionally, miR-3529-3p mitigated chemoresistance by inhibiting the Wnt signaling pathway through positively regulating HOOK3 expression. In summary, miR-3529-3p in exosomes plays a crucial role in overcoming trastuzumab resistance, highlighting its potential as both a therapeutic target and a prognostic marker for individuals with breast Cancer.

Breast cancer; Exosomes; Trastuzumab; Wnt/β-catenin signaling; miR-3529-3p.