Background and purpose: As the targeted antibody of human epidermal growth factor receptor 2 (HER2)

trastuzumab resistance gets more and more attention. This study aimed to explore the role of miR-375 in the occurrence of trastuzumab resistance in breast cancer cells through regulating epithelial-mesenchymal transition (EMT) by targeting Yes-associated protein 1 (YAP1). Methods: Trastuzumab-resistant breast cancer cell line was established. miR-375 mimic and recombinant plasmid YAP1 were transfected into SK-BR-3R cells. The sensitivities of each breast cancer cell line to trastuzumab were detected by MTT assay

and proliferation was detected by colony formation assay. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) and Western blot were applied to detect mRNA and protein expressions of miR-375

vimentin

E-cadherin and YAP1. Dual-luciferase reporter gene assay was conducted to verify the role of miR-375 in regulation of YAP1 transcription. A total of 25 breast cancer tissues from patients were collected to detect correlation in clinical performance. Results: Compared with NC group

after transfection with miR-375 mimic

the sensitivity to trastuzumab (P0.01) and capacity of colony formation (P0.01) for SK- BR-3R (resistance) cell line were decreased significantly

and the expression of vimentin was significantly downregulated

whereas E-cadherin was significantly upregulated (all P0.05). YAP1 as downstream target gene of miR-375 was observed (P0.01). MiR- 375 was negatively correlated with YAP1 in breast cancer tissues (r=-0.586 8

P=0.002 8). After miR-375 mimic and YAP1-MUT co- transfection in SK-BR-3R

compared with the control

the sensitivity to trastuzumab (P0.01)

capacity of colony formation (P0.05) and the expressions of vimentin and E-cadherin were restored (P0.05). Conclusion: miR-375 takes part in trastuzumab resistance of breast cancer cells through regulating EMT

which is mediated by targeting YAP1.