tumor tissues; plasma; plasma-derived EVs
MDA-MB-231; MDA-MB-231/ADR
cell line-derived xenograft
proliferation (promotes); migration (promotes); invasion (promotes); apoptosis (inhibits); metastasis (promotes); ceRNA regulation (promotes); m6A modification (promotes); drug resistance (promotes); chemoresistance (promotes); mRNA stability (other)
RNase R Treatment; Actinomycin D / DRB Stability Assay; RT-qPCR; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); Luciferase Reporter Assay; Transfection; CCK8; Colony Formation Assay; Transwell Assay; In Vivo Animal Model; IHC (Immunohistochemistry); Western Blot; ROC Analysis; Bioinformatics Analysis
EV-circSEPT9 is a stable and quantifiable biomarker with potential utility for predicting DOX resistance in TNBC; ROC AUC = 0.904, sensitivity 69.23%, specificity 96.77%.
circSEPT9 is upregulated in DOX-resistant TNBC tissues, cells, plasma, and EVs. LDHA Y10 phosphorylation promotes EV-mediated circSEPT9 release and transfer to sensitive TNBC cells, where circSEPT9 sponges miR-515-5p, upregulates KIAA1429, enhances m6A methylation, and promotes proliferation, invasion, tumor growth, and chemoresistance. EV-circSEPT9 also shows diagnostic potential for identifying DOX resistance in TNBC.
0.8655
Y10 phosphorylation of LDHA promotes the release of extracellular vesicle-derived circSEPT9 to enhance the chemoresistance of triple negative breast cancer cells via modulation of the miR-515-5p/KIAA1429 axis.
combined biological and clinical study