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MicroRNA-335 inhibits invasion and metastasis of colorectal cancer by targeting ZEB2

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Abstract

MicroRNAs have been suggested to play a vital role in regulate tumor progression and invasion. However, the expression of miR-335 in colorectal cancer (CRC) and its clinical significance are not known. Here, we report that miR-335 is a tumor suppressor by regulating expression of ZEB2. In this study, we showed that downregulated miR-335 levels in highly invasive CRC cell lines and tissues. Kaplan–Meier survival analysis indicated that patients with reduced miR-335 had a poor overall survival. Furthermore, enhancing the expression of miR-335 inhibited CRC cell migration and invasion in vitro and lung and liver metastasis in vivo, while silencing its expression resulted in increased migration and invasion. Additionally, we identified a novel miR-335 target, ZEB2, and the direct interaction between them was verified by 3′-untranslated region dual-luciferase reporter assay. In conclusion, our results demonstrate that miR-335 functions as a tumor suppressor and play a role in inhibiting metastasis of CRC cells through targeting ZEB2. These findings suggest that miR-335 may be useful as a new potential therapeutic target for CRC.

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Ethical standards

The use of tissues for this study has been approved by the ethics committee of Tang Du Hospital, Fourth Military Medical University. All of the patients signed the informed consent before use of these clinical materials for research purposes. This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Committee on the Ethics of Animal Experiments of Fourth Military Medical University.

Acknowledgments

Supported by the National Natural Science Foundation of China, No. 81171984.

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Department of Gastrointestinal Surgery, Xi Jing Digestive Hospital, Fourth Military Medical University, Xi’an, Shan Xi Province, China

    ZhiFeng Sun

  2. Department of General Surgery, Tang Du Hospital, Fourth Military Medical University, Xi’an, Shan Xi Province, China

    Zhang Zhang & Bo Qiu

  3. Experimental Teaching Center, Fourth Military Medical University, Xi’an, Shan Xi Province, China

    Zidong Liu

  4. Department of Foreign Languages, School of Basic Medical Sciences, Fourth Military Medical University, Xi’an, Shan Xi Province, China

    Kan Liu

  5. Department of General Surgery, The General Hospital of PLA, Bei Jing, China

    Guanglong Dong

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  1. ZhiFeng Sun
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  4. Bo Qiu
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  5. Kan Liu
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Corresponding author

Correspondence to Guanglong Dong.

Additional information

ZhiFeng Sun, Zhang Zhang and Zidong Liu have contributed equally to this study, and all should be considered first author.

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Sun, Z., Zhang, Z., Liu, Z. et al. MicroRNA-335 inhibits invasion and metastasis of colorectal cancer by targeting ZEB2. Med Oncol 31, 982 (2014). https://doi.org/10.1007/s12032-014-0982-8

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  • DOI: https://doi.org/10.1007/s12032-014-0982-8

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