China Oncology ›› 2021, Vol. 31 ›› Issue (1): 27-34.doi: 10.19401/j.cnki.1007-3639.2021.01.004

• Article • Previous Articles     Next Articles

miR-375 targeting YAP1 modulates trastuzumab resistance through epithelial-mesenchymal transition in breast cancer cells

YE Xingming 1 , WANG Lin 1 , JIA Jing 1 , WU Xiufeng 2 , CHEN Ying 1   

  1. 1. Central Laboratory, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou 350014, Fujian Province, China; 2. Breast Surgery, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou 350014, Fujian Province, China
  • Online:2021-01-30 Published:2021-02-20
  • Contact: CHEN Ying E-mail:

Abstract: 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 (P<0.01) and capacity of colony formation (P<0.01) 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 P<0.05). YAP1 as downstream target gene of miR-375 was observed (P<0.01). 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 (P<0.01), capacity of colony formation (P<0.05) and the expressions of vimentin and E-cadherin were restored (P<0.05). Conclusion: miR-375 takes part in trastuzumab resistance of breast cancer cells through regulating EMT, which is mediated by targeting YAP1.

Key words: miR-375, Trastuzumab resistance, Breast cancer, Yes-associated protein 1, Epithelial-mesenchymal transition