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miR-200c inhibits TGF-beta-induced-EMT to restore trastuzumab sensitivity by targeting ZEB1 and ZEB2 in gastric cancer

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机构: [1]Department of Oncology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, People’s Republic of China [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 [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
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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.

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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
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出版当年[2018]版:
Q1 GENETICS & HEREDITY Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q1 MEDICINE, RESEARCH & EXPERIMENTAL Q2 ONCOLOGY
最新[2024]版:
Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q1 GENETICS & HEREDITY Q1 MEDICINE, RESEARCH & EXPERIMENTAL Q1 ONCOLOGY

影响因子: 最新[2024版] 最新五年平均 出版当年[2018版] 出版当年五年平均 出版前一年[2017版] 出版后一年[2019版]

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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
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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
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