Fig 1: SF3B4 (sap-49) packages miR-216a-5p into 4T1 exosomes. a Three candidate proteins were screened from RBPBD. b The effect of SF3B4 knockdown in 4T1 cells was assessed via western blotting. c The miR-216a-5p level in cell lysates and EXOs was analyzed via qRT‒PCR. d The SF3B4 binding motif and the matched miR-216a-5p sequence. e The binding of the wild-type and mutated miR-216a-5p probes to SF3B4 in 4T1 cells and EXOs from 4T1 cells was measured using an RNA pull-down assay. f The identified motif was the genuine binding region of miR-216a-5p and SF3B4, and mutated versions of miR-216a-5p were tested for binding to SF3B4 via EMSA. g SF3B4 in 4T1 cells was knocked down, and EXOs were isolated. After adult murine ventricular cardiomyocytes (AMVCs) were incubated with 4T1-derived EXOs containing Cy3-miR-216a-5p, Cy3 fluorescence in AMVCs was detected. Scale bar: 20 μm. h AMVCs were treated with SF3B4-knockdown and DOX-exposed 4T1 BCC-EXOs and exposed to DOX. The viability of AMVCs was assessed using CCK-8 assays (n = 5). i–k LDH release and IL-18 and IL-1β levels in AMVCs were assessed using a colorimetric method (n = 5). “siNC-BCC-EXOs” indicates exosomes from control siRNA-transfected DOX-induced 4T1 cells, “siSF3B4-BCC-EXOs” denotes exosomes from SF3B4-knockdown DOX-induced 4T1 cells, “BCCs” denotes breast cancer cells, “ns” indicates non-significant, and “DOX” indicates doxorubicin. Data are presented as means ± SD