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

ABSTRACT

Background: 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.