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

Amini-Farsani, Zeinab. and Sangtarash, Mohammad Hossein. and Shamsara, Mehdi. and Teimori, Hossein. (2017) MiR-221/222 promote chemoresistance to cisplatin in ovarian cancer cells by targeting PTEN/PI3K/AKT signaling pathway. Cytotechnology. ISSN 0920-9069

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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.

Item Type: Article
Uncontrolled Keywords: Keywords Cisplatin MiR-221/222 PTEN Ovarian cancer Apoptosis In
Subjects: QT physiology
WP Gynecology
QZ pathology-Neoplasms
Divisions: Reserach Vice-Chancellar Department > Cellular and Molecular Research Center
Depositing User: zahra bagheri .
Date Deposited: 20 Sep 2017 03:11
Last Modified: 24 Feb 2018 06:20
URI: http://eprints.skums.ac.ir/id/eprint/5358

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