Fig. 7
Mechanism of the biomarkers for trastuzumab treatment resistance. a–d SKBR3 and BT474 were transduced with nc, ASO, or mimics of four miRNAs, then trastuzumab was added to the medium at 10 μg ml−1 for 3 days, MTS assay was used to compare cell proliferation/apoptosis of treated cells (mean + s.e.m., n = 5 independent experiments; **P < 0.01; ***P < 0.001. P-values were obtained using two-tailed Student’s t-test). e TargetScan and MicroTar predicted PTEN as the target gene of miR-940, IGF1R as the target gene of miR-16-5p and miR-451a, and SRC as the target gene of miR-17-3p. Target sequences and their mutant forms of PTEN, IGF1R, and SRC in 3′UTR were synthesized and subcloned into pGL3 promoter vector. f–i Luciferase reporter assays for SKBR3 cells transfected with pGL3 promoter vectors carrying PTEN-3′UTR vs PTEN-mut-3′UTR, IGF1R-3′UTR vs IGF1R-mut-3′UTR or SRC-3′UTR vs SRC-mut-3′UTR in the absence or presence of the indicated miRNA mimics. (mean + s.e.m., n = 5 independent experiments; **P < 0.01; ***P < 0.001 compare to untreated cells by two-tailed Student’s t-test)
