Fig. 6

Chemo-toxicity promotes miR-378a-3p and miR-378d secretion from chemo-treated breast cancer cells by activating the EZH2/STAT3 pathway. a Western blot detection of changes in the protein expression of EZH2 and STAT3 after 4 h of PBS, DOX or PTX treatment. b–e CAL51 cells transfected with si. EZH2 or si.NC for 48 h followed by 4 h of DOX or PTX treatment. b Changes in miR-378a-3p and miR-378d expression in CAL51 cells after transfection and drug treatment. c Changes in miR-378a-3p and miR-378d expression in exosomes after transfection and drug treatment. d, e Exosomes induced by CAL51 cells after transfection and drug treatments were co-cultured with untreated cells. d Evaluation of the effect of DOX and PTX on cell viability. e Sphere formation assay analysis. f The expression level of miR-378 was positively correlated with STAT3 in breast cancer (n = 470). g According to the potential binding site, the miR-378a-3p promoter was divided into three segments: − 560 to − 380 for blue, − 380 to − 230 for orange and − 230 to − 60 for red. The miR-378d promoter was divided into four segments: − 910 to − 800 for blue, − 800 to − 520 for orange, − 520 to − 230 for red and − 320 to − 65 for green. (H) Chromatin immunoprecipitation experiments to analyze STAT3 binding to miR-378a-3p and miR-378d promoters. (I–L) CAL51 cells transfected with si. STAT3 or si.NC for 48 h followed by 4 h of DOX or PTX treatment. i Changes in miR-378a-3p and miR-378d expression in CAL51 cells after transfection and drug treatment. j Changes in miR-378a-3p and miR-378d expression in exosomes after transfection and drug treatment. k, l Exosomes induced by CAL51 cells after transfection and drug treatments were co-cultured with untreated cells. k Evaluation of the effect of DOX and PTX on cell viability. l CD44+/CD24- population analysis. *p < 0.05, ** p < 0.01, *** p < 0.001