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

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-...

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Bibliographic Details
Published in:Cytotechnology (Dordrecht) 2018-02, Vol.70 (1), p.203-213
Main Authors: Amini-Farsani, Zeinab, Sangtarash, Mohammad Hossein, Shamsara, Mehdi, Teimori, Hossein
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
AKT protein
Apoptosis
Biochemistry
Biomedicine
Biotechnology
Cell cycle
Cell viability
Chemistry
Chemistry and Materials Science
Chemoresistance
Cisplatin
Cytotoxicity
Down-regulation
Drug resistance
Genes
MicroRNAs
Ovarian cancer
PTEN protein
Signal transduction
Software
Statistical analysis
Therapeutic targets
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Summary: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.
ISSN:0920-9069
1573-0778
DOI:10.1007/s10616-017-0134-z