MicroRNA-218 regulates the chemo-sensitivity of cervical cancer cells through targeting survivin

• Main Authors: Yu M, Xu B, Yang H, Xue S, Zhang R, Zhang H, Ying X, Dai Z
• Format: Article
• Language: English
• Published: Dove Medical Press 2019-07-01
• Series: Cancer Management and Research
• Subjects: miR-218; cervical cancer; cisplatin resistant; apoptosis; survivin
• Online Access: https://www.dovepress.com/microrna-218-regulates-the-chemo-sensitivity-of-cervical-cancer-cells--peer-reviewed-article-CMAR

Minmin Yu,1,2,* Baozhen Xu3,*, Hui Yang4,*, Songlin Xue,2 Rong Zhang,2 Hongmei Zhang,5 Xiaoyan Ying,1 Zhiqin Dai61Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, People’s Republic of China; 2Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing 210003, People’s Republic of China; 3Department of Obstetrics and Gynecology, Nanjing Lishui People’s Hospital, Nanjing 211200, People’s Republic of China; 4Department of Obstetrics and Gynecology, Huaian Maternal and Child Health Care Hospital, Huaian 223002, People’s Republic of China; 5Department of Clinical Research Center, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing 210003, People’s Republic of China; 6Department of Gynecologic Oncology, Jiangsu Cancer Hospital, Nanjing 210009, People’s Republic of China*These authors contributed equally to this workBackground: Cervical cancer is one of the most lethal malignancies among women in the world. Every year about 311,365 women die because of cervical cancer. Chemo-resistance is the main reason of the lethal malignancies, and the mechanism of chemo-resistance in cervical cancer still remains largely elusive.Purpose: Previous studies reported that microRNAs played important biological roles in the chemo-resistance in many types of cancers, in the present study we tried to investigate the biological roles of microRNA-218 in chemo-resistance in cervical cancer cells.Results: Real-time PCR results indicated microRNA-218 was downregulated in cisplatin-resistant HeLa/DDP and SiHa/DDP cells compared with the mock HeLa and SiHa cells. CCK-8 assay results showed upregulation of microRNA-218 enhanced the cisplatin sensitivity of cervical cancer cells; while downregulation of microRNA-218 decreased the cisplatin sensitivity of cervical cancer cells. Dual-luciferase assay indicated survivin was a direct target of microRNA-218. Western blotting and PCR results indicated the expression of survivin in HeLa/DDP and SiHa/DDP cells was significantly increased compared with HeLa and SiHa cells. Further study indicated induction of microRNA-218 decreased the expression of survivin while inhibition of microRNA-218 increased the expression of survivin in cervical cancer cells. Cell apoptosis results indicated induction of microRNA-218 induced the cell apoptosis in cervical cancer cells.Conclusion: Our data revealed microRNA-218 enhanced the cisplatin sensitivity in cervical cancer cells through regulation of cell growth and cell apoptosis, which could potentially benefit to the cervical cancer treatment in the future.Keywords: miR-218, cervical cancer, cisplatin resistant, apoptosis, survivin