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MiR-221/222 promote chemoresistance to cisplatin in ovarian cancer cells by targeting PTEN/PI3K/AKT signaling pathway

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Abstract

Cisplatin resistance is one of the main limitations in the treatment of ovarian cancer, and its mechanism has not been fully understood. The objectives of this study were to determine the role of miR-221/222 and its underlying mechanism in chemoresistance of ovarian cancer. We demonstrated that miR-221/222 expression levels were higher in A2780/CP cells compared with A2780 S cells. An in vitro cell viability assay showed that downregulation of miR-221/222 sensitized A2780/CP cells to cisplatin-induced cytotoxicity. Moreover, we found that knockdown of miR-221/222 by its specific inhibitors promoted the cisplatin-induced apoptosis in A2780/CP cells. Using bioinformatic analysis and luciferase reporter assay, miR-221/222 were found to directly target PTEN. Moreover, knockdown of miR-221/222 in A2780/CP cells significantly upregulated PTEN and downregulated PI3KCA and p-Akt expression. In conclusion, our results demonstrated that miR-221/222 induced cisplatin resistance by targeting PTEN mediated PI3K/Akt pathway in A2780/CP cells, suggesting that miR-221/222/PTEN/PI3K/Akt may be a promising prognostic and therapeutic target to overcome cisplatin resistance and treat ovarian cancer in the future.

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Acknowledgements

This work was supported by Shahrekord University of Medical Sciences, Shahrekord, Iran (Research Grant: 1837). We would also like to acknowledge the staffs at the Cellular and Molecular Research Center for their sincere cooperation.

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Authors and Affiliations

  1. Department of Biology, University of Sistan and Baluchestan, Zahedan, Iran

    Zeinab Amini-Farsani & Mohammad Hossein Sangtarash

  2. National Research Center for Transgenic Mouse, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran

    Mehdi Shamsara

  3. Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, 8813833435, Rahmatiyeh, Shahrekord, Iran

    Hossein Teimori

Authors
  1. Zeinab Amini-Farsani
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  2. Mohammad Hossein Sangtarash
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  3. Mehdi Shamsara
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  4. Hossein Teimori
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Correspondence to Hossein Teimori.

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Amini-Farsani, Z., Sangtarash, M.H., Shamsara, M. et al. MiR-221/222 promote chemoresistance to cisplatin in ovarian cancer cells by targeting PTEN/PI3K/AKT signaling pathway. Cytotechnology 70, 203–213 (2018). https://doi.org/10.1007/s10616-017-0134-z

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  • DOI: https://doi.org/10.1007/s10616-017-0134-z

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