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

Cancer Gene Therapy volume 25, pages 68–76 (2018)Cite this article

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A Correction to this article was published on 05 November 2020

This article has been updated

Abstract

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-β, 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-β 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-β/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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Change history

  • 22 October 2020

    The original version of this Article contained inaccuracies in Fig. 2a and 4d (one micrograph has been duplicated and presented as something else), Fig. 2b and 4c (one micrograph has been duplicated and presented as something else) and Fig 3b and 4j (the two beta-actin bands are more similar than you would expect). All figures have been corrected in both the PDF and HTML versions of the Article.

    Figure 4d: A large number of wound-healing assays graphs were taken, and had been taken as the cell control for the NCI-N87 ( NCI-N87 and NCI-N87 NC), however there was negligence and repetition in the naming of the pictures. Therefore, these eventually led to the wrong insertion of the image when the authors prepared the figures. One image was repeated in Figure 2A and Figure 4D. Figure 4D has been corrected.

    Figure 4c: Due to a large number of invasion assay photos taken and similarity of images, there was an error during image selection when the authors prepared the figure. The NCI-N87 results were used in NCI-N87-200c inhibitors group. One micrograph in Figure 2C and Figure 4C has been duplicated. Figure 4C has been corrected.

    Figures 3b and 4j: The two beta-actin bands in Figure 3B and Figure 4J were very similar. We provided the original image. The extreme similarity of the bands does raise doubts. Therefore, the authors have provided two other images and modified Figure 3B and Figure 4J to eliminate these doubts.

  • 05 November 2020

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Acknowledgements

This study was supported by Key Project of Health and Family Planning Commission of Hebei Province (No: 20170150) and Hebei Science and Technology project (No: 162777138). We thank Dr. Nathanael Herz Green from Baylor College of Medicine for proofreading and critical comments on the manuscript.

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Authors and Affiliations

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

    Xinliang Zhou, Jing Han, Zhisong Fan, Yudong Wang, Yalei Lv & Jing Zuo

  2. Department of Pediatrics, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China

    Xinyi Men

  3. Research Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China

    Riyang Zhao, Lianmei Zhao, Meixiang Sang & Baoen Shan

  4. Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Xian-De Liu

  5. Tumor Research Institute, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China

    Baoen Shan

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  1. Xinliang Zhou
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Zhou, X., Men, X., Zhao, R. et al. miR-200c inhibits TGF-β-induced-EMT to restore trastuzumab sensitivity by targeting ZEB1 and ZEB2 in gastric cancer. Cancer Gene Ther 25, 68–76 (2018). https://doi.org/10.1038/s41417-017-0005-y

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