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Restoration of microRNA-708 sensitizes ovarian cancer cells to cisplatin via IGF2BP1/Akt pathway.
Cell Biol Int. 2017 Oct; 41(10):1110-1118.CB

Abstract

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 two- to threefold. miR-708 overexpression significantly augmented cisplatin-induced apoptosis in ovarian cancer cells, which was coupled with increased caspase-3 activity by two- to fourfold. 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 three- and fivefold, 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.

Authors+Show Affiliations

Department of Obstetrics and Gynecology, Liaocheng People's Hospital, Liaocheng, People's Republic of China.Department of Obstetrics and Gynecology, Liaocheng People's Hospital, Liaocheng, People's Republic of China.Department of Obstetrics and Gynecology, Dezhou People's Hospital, Dezhou, People's Republic of China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28685895

Citation

Qin, Xuying, et al. "Restoration of microRNA-708 Sensitizes Ovarian Cancer Cells to Cisplatin Via IGF2BP1/Akt Pathway." Cell Biology International, vol. 41, no. 10, 2017, pp. 1110-1118.
Qin X, Sun L, Wang J. Restoration of microRNA-708 sensitizes ovarian cancer cells to cisplatin via IGF2BP1/Akt pathway. Cell Biol Int. 2017;41(10):1110-1118.
Qin, X., Sun, L., & Wang, J. (2017). Restoration of microRNA-708 sensitizes ovarian cancer cells to cisplatin via IGF2BP1/Akt pathway. Cell Biology International, 41(10), 1110-1118. https://doi.org/10.1002/cbin.10819
Qin X, Sun L, Wang J. Restoration of microRNA-708 Sensitizes Ovarian Cancer Cells to Cisplatin Via IGF2BP1/Akt Pathway. Cell Biol Int. 2017;41(10):1110-1118. PubMed PMID: 28685895.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Restoration of microRNA-708 sensitizes ovarian cancer cells to cisplatin via IGF2BP1/Akt pathway. AU - Qin,Xuying, AU - Sun,Linlin, AU - Wang,Jing, Y1 - 2017/08/17/ PY - 2017/03/07/received PY - 2017/07/05/accepted PY - 2017/7/8/pubmed PY - 2018/3/22/medline PY - 2017/7/8/entrez KW - apoptosis KW - chemoresistance KW - microRNA KW - ovarian cancer KW - target SP - 1110 EP - 1118 JF - Cell biology international JO - Cell Biol. Int. VL - 41 IS - 10 N2 - 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 two- to threefold. miR-708 overexpression significantly augmented cisplatin-induced apoptosis in ovarian cancer cells, which was coupled with increased caspase-3 activity by two- to fourfold. 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 three- and fivefold, 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. SN - 1095-8355 UR - https://www.unboundmedicine.com/medline/citation/28685895/Restoration_of_microRNA_708_sensitizes_ovarian_cancer_cells_to_cisplatin_via_IGF2BP1/Akt_pathway_ L2 - https://doi.org/10.1002/cbin.10819 DB - PRIME DP - Unbound Medicine ER -