BANCR-containing extracellular vesicles enhance breast cancer resistance.

Extracellular vesicles (EVs) are nano-sized particles secreted by many cell types-including tumor cells-and play key roles in cellular communication by transporting functional RNAs. This study aims to elucidate the role of long noncoding RNA BRAF-activated nonprotein coding RNA (BANCR) in EVs derived from breast cancer (BC) cells in trastuzumab resistance. Differentially expressed long noncoding RNA and downstream targets in BC-resistant samples were identified. SKBR-3 cells were treated with trastuzumab to generate resistant cells (SKBR-3TR), and EVs from these cells (SKBR-3TR-EVs) were isolated and characterized. Functional studies of BANCR were performed in SKBR-3 and SKBR-3TR cells. Coculturing SKBR-3 cells with SKBR-3TR-EVs assessed changes in cell behavior. A xenograft model in nude mice examined in vivo tumorigenicity and trastuzumab resistance. BANCR was highly expressed in SKBR-3TR cells and EVs, linked to trastuzumab resistance. SKBR-3TR-EVs transferred BANCR to SKBR-3 cells, where BANCR inhibited miR-34a-5p, reducing its expression. High-mobility group A1 (HMGA1) was identified as a miR-34a-5p target. BANCR activated the HMGA1/Wnt/β-catenin pathway by inhibiting miR-34a-5p, promoting resistance. In vivo experiments showed that BANCR inhibition delayed tumorigenesis and reversed trastuzumab resistance. BC cell-derived EVs containing BANCR may enhance resistance to trastuzumab by regulating the miR-34a-5p/HMGA1/Wnt/β-catenin axis, presenting a potential target for BC therapy.