, Volume 70, Issue 1, pp 203–213 | Cite as

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

  • Zeinab Amini-Farsani
  • Mohammad Hossein Sangtarash
  • Mehdi Shamsara
  • Hossein TeimoriEmail author


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.


Cisplatin MiR-221/222 PTEN Ovarian cancer Apoptosis 



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.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interests.


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Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  • Zeinab Amini-Farsani
    • 1
  • Mohammad Hossein Sangtarash
    • 1
  • Mehdi Shamsara
    • 2
  • Hossein Teimori
    • 3
    Email author
  1. 1.Department of BiologyUniversity of Sistan and BaluchestanZahedanIran
  2. 2.National Research Center for Transgenic MouseNational Institute of Genetic Engineering and BiotechnologyTehranIran
  3. 3.Cellular and Molecular Research Center, Basic Health Sciences InstituteShahrekord University of Medical SciencesRahmatiyeh, ShahrekordIran

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