Restoration of microRNA-708 sensitizes ovarian cancer cells to cisplatin via IGF2BP1/Akt pathway
| Autor: | Linlin Sun, Xuying Qin, Jing Wang |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cisplatin endocrine system diseases Cell Biology General Medicine Transfection Biology medicine.disease 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Apoptosis 030220 oncology & carcinogenesis medicine Cancer research Phosphorylation Metastasis suppressor Ovarian cancer Protein kinase B PI3K/AKT/mTOR pathway medicine.drug |
| Zdroj: | Cell Biology International. 41:1110-1118 |
| ISSN: | 1065-6995 |
| DOI: | 10.1002/cbin.10819 |
| Popis: | A previous study has shown that microRNA-708 (miR-708) functions as a metastasis suppressor in ovarian cancer. In this study, we aimed to explore its implication in regulating cisplatin sensitivity in ovarian cancer cells. To this end, ovarian cancer cells were transfected with miR-708-expressing plasmids or vector before treatment with different concentrations of cisplatin for 48 h. The 50% inhibitory concentration (IC50) value was calculated. Apoptosis was analyzed by measuring caspase-3 activity. The target gene mediating the function of miR-708 was identified. Ectopic expression of miR-708 sensitized SKOV3 and A2780 cells to cisplatin, decreasing the IC50 value by 2-3-fold. miR-708 overexpression significantly augmented cisplatin-induced apoptosis in ovarian cancer cells, which was coupled with increased caspase-3 activity by 2-4-fold. Similarly, overexpression of miR-708 increased the sensitivity of cisplatin-resistant SKOV3/DDP and A2780/DDP cells to cisplatin-induced toxicity, reducing the IC50 by 3- and 5-fold, respectively. Delivery of miR-708 enhanced cisplatin-induced elevation in caspase-3 activity in both cisplatin-resistant and parental ovarian cancer cells. Mechanistically, miR-708 downregulated the expression of insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) and suppressed Akt phosphorylation. Silencing of IGF2BP1 markedly blocked the phosphorylation of Akt. Overexpression of IGF2BP1 restored cisplatin resistance and Akt phosphorylation in miR-708-overexpressing ovarian cancer cells. Collectively, miR-708 increases the susceptibility of ovarian cancer cells to cisplatin by targeting IGF2BP1 and inhibiting Akt signaling. Delivery of miR-708 may represent a promising strategy for improving cisplatin chemotherapy. |
| Databáze: | OpenAIRE |
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