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

被引：0

作者：

Zeinab Amini-Farsani

Mohammad Hossein Sangtarash

Mehdi Shamsara

Hossein Teimori

机构：

[1] University of Sistan and Baluchestan,Department of Biology

[2] National Institute of Genetic Engineering and Biotechnology,National Research Center for Transgenic Mouse

[3] Shahrekord University of Medical Sciences,Cellular and Molecular Research Center, Basic Health Sciences Institute

来源：

Cytotechnology | 2018年 / 70卷

关键词：

Cisplatin; MiR-221/222; PTEN; Ovarian cancer; Apoptosis;

D O I：

暂无

中图分类号：

学科分类号：

摘要：

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.

引用

页码：203 / 213

页数：10

共 256 条

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