Fig. 8

CAF-derived exosomal miR-196a enhances cisplatin resistance in HNC cells in vivo. a CAL 27 cells with or without CAFs were used to establish a xenograft mouse model. The mice were intraperitoneally injected with cisplatin (4 mg/kg, every 4 days) with or without GW4869 (2 mg/kg, every 2 days). The tumor growth curve, tumor volumes, and tumor weights are shown. b CAL 27 cells were stably transfected with or without miR-196a, and CAFs were stably transfected with miR-196a or anti-miR-196a. Nude mice were subcutaneously xenografted with pre-transfected CAL 27 cells or CAFs as indicated. The mice were intraperitoneally injected 5 times with cisplatin (4 mg/kg, every 4 days). The tumor growth curve, tumor volumes, and tumor weights are shown. c Upregulated miR-196a levels were correlated with increased tumor size, lymph node metastasis, and advanced tumor stage in HNC tissues. d Real-time PCR analysis showing miR-196a expression in HNC tissues from chemosensitive patients (n = 20) and chemoresistant patients (n = 20). e Kaplan-Meier analysis of overall survival. Compared with patients with low miR-196a expression, patients with high miR-196a expression had a significantly lower overall survival rate. f Plasma exosomal miR-196a levels were detected using real-time PCR with plasma from HNC patients and healthy donors. g Real-time PCR analysis of exosomal miR-196a in matched plasma from HNC patients pre- and postoperation (n = 40). h Real-time PCR analysis of exosomal miR-196a expression in the plasma of chemosensitive patients (n = 20) and chemoresistant patients (n = 20). i Kaplan-Meier analysis of overall survival in 74 HNC patients from high and low miR-196a groups, according to the median exosomal miR-196a level in pre-therapy plasma. j ROC curve analysis of plasma exosomal miR-196a expression for discriminating the chemoresistant group (n = 20) from the chemosensitive group (n = 20). AUC, area under the curve. k A proposed model illustrating the modulatory role of CAF-derived exosomal miR-196a in regulating HNC cell proliferation and cisplatin resistance. (*p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001)