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Published on: February 21, 2014
MicroRNA-218 regulates the chemo-sensitivity of cervical cancer cells through targeting survivin
Minmin Yu1,2, Baozhen Xu3, Hui Yang4
1Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, People's Republic of China.
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.
Insights
MicroRNA-218 enhances cisplatin sensitivity in cervical cancer by targeting survivin, promoting apoptosis, and improving treatment outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cervical cancer is a leading cause of death in women globally, with chemo-resistance hindering effective treatment.
- The mechanisms underlying chemo-resistance in cervical cancer remain poorly understood.
- MicroRNAs are implicated in cancer chemo-resistance, prompting investigation into their specific roles.
Purpose of the Study:
- To investigate the role of microRNA-218 in chemo-resistance within cervical cancer cells.
- To determine if microRNA-218 influences sensitivity to cisplatin, a common chemotherapy drug.
- To identify potential molecular targets of microRNA-218 involved in chemo-resistance.
Main Methods:
- Real-time PCR to quantify microRNA-218 levels in cisplatin-resistant and sensitive cell lines.
- CCK-8 assays to assess the impact of microRNA-218 modulation on cisplatin sensitivity.
- Dual-luciferase reporter assays to validate survivin as a direct target of microRNA-218.
- Western blotting and PCR to analyze survivin and apoptosis-related protein expression.
- Cell apoptosis assays to evaluate the effect of microRNA-218 on programmed cell death.
Main Results:
- MicroRNA-218 was significantly downregulated in cisplatin-resistant cervical cancer cells (HeLa/DDP, SiHa/DDP).
- Upregulating microRNA-218 increased cisplatin sensitivity, while downregulation decreased it.
- Survivin was identified as a direct target of microRNA-218, with its expression inversely correlated to microRNA-218 levels.
- MicroRNA-218 induction promoted cervical cancer cell apoptosis.
Conclusions:
- MicroRNA-218 plays a crucial role in enhancing cisplatin sensitivity in cervical cancer.
- The mechanism involves the regulation of survivin expression, cell growth, and apoptosis.
- MicroRNA-218 represents a potential therapeutic target for improving cervical cancer treatment outcomes.
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