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Restoration of microRNA‐708 sensitizes ovarian cancer cells to cisplatin via IGF2BP1/Akt pathway
Author(s) -
Qin Xuying,
Sun Linlin,
Wang Jing
Publication year - 2017
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.10819
Subject(s) - cisplatin , ovarian cancer , protein kinase b , microrna , cancer research , ectopic expression , apoptosis , gene silencing , transfection , phosphorylation , chemistry , biology , microbiology and biotechnology , cancer , cell culture , medicine , gene , chemotherapy , biochemistry , genetics
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 (IC 50 ) 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 IC 50 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 IC 50 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.