机构：[1]Department of Oncology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, People’s Republic of China临床科室肿瘤内科河北医科大学第四医院[2]Department of Pediatrics, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, People’s Republic of China[3]Research Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, People’s Republic of China河北医科大学第四医院[4]Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA[5]Tumor Research Institute, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, People’s Republic of China河北医科大学第四医院
Gastric cancer is the fifth most common malignancy in the world, with Eastern Asia as one of areas with the highest incidence rates. Trastuzumab, a HER2-targeting antibody, combined with chemotherapy has been successfully employed for the gastric cancer patients with HER2 overexpression/amplification. However, trastuzumab resistance is a major problem in clinical practice. Here we observed that the trastuzumab-resistant gastric cancer cell line NCI-N87/TR expressed high levels of epithelial-mesenchymal transition factors and demonstrated increased migration and invasion capability compared with NCI-N87 cells. Downregulated E-cadherin and increased N-cadherin, TGF-beta, ZEB1, ZEB2, TWIST1, and Snail were detected in NCI-N87/TR cells. We also found that miR-200c was downregulated in NCI-N87/TR cells compared with parental cells NCI-87 by qRT-PCR. Treatment with TGF-beta downregulated the expression of miR-200c and upregulated ZEB2, and significantly decreased the trastuzumab sensitivity of NCI-N87 cells. miR-200c restored trastuzumab sensitivity and inhibited migration and invasion through suppressing ZEB1 and ZEB2. In summary, TGF-beta/ZEB2 axis plays an encouraging role in trastuzumab resistance of gastric cancer, while miR-200c overexpression downregulates ZEB1/ZEB2 and resensitizes drugs resistance. Our findings might provide a potential therapeutic strategy for trastuzumab resistance of gastric cancer.
基金：
Key Project of
Health and Family Planning Commission of Hebei Province (No:
20170150) and Hebei Science and Technology project (No:
162777138)
语种：
外文
被引次数：
WOS：
PubmedID：
中科院分区：
出版当年[2018]版：
大类|2 区医学
小类|3 区生物工程与应用微生物3 区遗传学3 区医学：研究与实验3 区肿瘤学
最新[2025]版：
大类|3 区医学
小类|3 区生物工程与应用微生物3 区遗传学3 区医学：研究与实验4 区肿瘤学
JCR分区：
出版当年[2018]版：
Q1GENETICS & HEREDITYQ1BIOTECHNOLOGY & APPLIED MICROBIOLOGYQ1MEDICINE, RESEARCH & EXPERIMENTALQ2ONCOLOGY
最新[2024]版：
Q1BIOTECHNOLOGY & APPLIED MICROBIOLOGYQ1GENETICS & HEREDITYQ1MEDICINE, RESEARCH & EXPERIMENTALQ1ONCOLOGY
第一作者机构：[1]Department of Oncology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, People’s Republic of China
通讯作者：
通讯机构：[3]Research Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, People’s Republic of China[5]Tumor Research Institute, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, People’s Republic of China
推荐引用方式(GB/T 7714)：
Zhou Xinliang,Men Xinyi,Zhao Riyang,et al.miR-200c inhibits TGF-beta-induced-EMT to restore trastuzumab sensitivity by targeting ZEB1 and ZEB2 in gastric cancer[J].CANCER GENE THERAPY.2018,25(3-4):68-76.doi:10.1038/s41417-017-0005-y.
APA：
Zhou, Xinliang,Men, Xinyi,Zhao, Riyang,Han, Jing,Fan, Zhisong...&Shan, Baoen.(2018).miR-200c inhibits TGF-beta-induced-EMT to restore trastuzumab sensitivity by targeting ZEB1 and ZEB2 in gastric cancer.CANCER GENE THERAPY,25,(3-4)
MLA：
Zhou, Xinliang,et al."miR-200c inhibits TGF-beta-induced-EMT to restore trastuzumab sensitivity by targeting ZEB1 and ZEB2 in gastric cancer".CANCER GENE THERAPY 25..3-4(2018):68-76
