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miR-200c modulates ovarian cancer cell metastasis potential by targeting zinc finger E-box-binding homeobox 2 (ZEB2) expression

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Abstract

This study was to investigate the effect of miR-200c on regulation of ovarian cancer cell metastasis potential and explore the underlying molecular events. qRT-PCR was used to analyze the level of miR-200c expression in 48 ovarian cancer and 30 normal ovarian tissue samples. pre-miR-200c was used to manipulate miR-200c expression in ovarian cancer cells for detection of changed phenotypes of tumor cells. Bioinformatics analysis was then used to predict target genes of miR-200c and GO and pathway analyses drew the miR-200c-related gene network. Luciferase reporter assay confirmed the target of miR-200c as ZEB2. Western blot was used to detect gene expressions in ovarian cancer cells. Level of miR-200c expression was much higher in ovarian cancer than in normal ovarian tissues, and miR-200c expression was inversely associated with advanced clinical stage and lymph node metastasis of ovarian cancer (p < 0.01). The database search predicted 186 miR-200c-targeting genes, and GO analysis showed that functions of these target genes were enriched in the protein binding and other biological processes. Furthermore, miR-200c expression inhibited ovarian cancer cell ES-2 migration and invasion capacity by suppression of ZEB2 expression (p < 0.01). Overexpression of miR-200c regulated E-cadherin and vimentin expression in ovarian cancer cells. This study demonstrated high miR-200c expression in ovarian cancer tissues and ZEB2 as a targeting gene of miR-200c, which mediated the effects of miR-200c on regulation of ovarian cancer cell migration and invasion capacity and epithelial-to-mesenchymal transition. Thus, targeting of miR-200c or ZEB2 may serve as a potential therapeutic strategy for control of ovarian cancer.

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Acknowledgments

This study was supported in part by Grants from National Natural Science Foundation of China (81001163), Liaoning Education Department for Scientific and Technological Research Project funds (2009A781), and Shenyang Science and Technology Project funds (F13-221-9-46).

Conflict of interest

The authors declared that there was no conflict of interest in this work.

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, The Affiliated Shengjing Hospital, China Medical University, Shenyang, 110003, China

    Yan-ming Lu, Yang-ling Ou, Duo Yin, Yi-Ning Li, Xiang Li, Ning Wang & Shu-lan Zhang

  2. Department of Neurobiology, China Medical University, Shenyang, China

    Chao Shang

  3. Institute of Pathology and Pathophysiology, China Medical University, Shenyang, China

    Chao Shang

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  1. Yan-ming Lu
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  2. Chao Shang
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  3. Yang-ling Ou
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Correspondence to Shu-lan Zhang.

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Lu, Ym., Shang, C., Ou, Yl. et al. miR-200c modulates ovarian cancer cell metastasis potential by targeting zinc finger E-box-binding homeobox 2 (ZEB2) expression. Med Oncol 31, 134 (2014). https://doi.org/10.1007/s12032-014-0134-1

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  • DOI: https://doi.org/10.1007/s12032-014-0134-1

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