Dataset Information

MicroRNA-186 induces sensitivity of ovarian cancer cells to paclitaxel and cisplatin by targeting ABCB1.

ABSTRACT:

Background

Recent studies have shown that microRNAs may regulate the ABCB1 gene (ATP-binding cassette, sub-family B [MDR/TAP], member 1). Computational programs have predicted that the 3'-untranslated region (3'-UTR) of ABCB1 contains a potential miRNA-binding site for miR-186. Here, we investigated the role of miR-186 in sensitizing ovarian cancer cells to paclitaxel and cisplatin.

Results

Human ovarian carcinoma cell lines OVCAR3, A2780, A2780/DDP, and A2780/Taxol were exposed to paclitaxel or cisplatin with or without miR-186 transfection, and cell viability was determined by MTT assay. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis were used to assess the MDR1, GST-?, and MRP1 expression levels. Dual-luciferase reporter assay was used to reveal the correlation between miR-186 and ABCB1. Lower miR-186 while higher MDR1 and GST-? mRNA expression levels were found in the A2780/Taxol and A2780/DDP cells than in the A2780 cells. After miR-186 transfection, all the cell lines showed increased sensitivity to paclitaxel and cisplatin. MiR-186 transfection induced apoptosis while anti-miR-186 transfection reduced apoptosis. The dual-luciferase reporter assay verified that that miR-186 combined with the 3'-untranslated region (UTR) of ABCB1. MDR1 and GST-? mRNA and protein expression levels were downregulated after transfection with miR-186 but upregulated following anti-miR-186 transfection compared to the mock and negative control cancer cells; however, the MRP1 expression levels did not significantly differ among the groups.

Conclusion

Our results are the first to demonstrate that miR-186 may sensitize ovarian cancer cell to paclitaxel and cisplatin by targeting ABCB1 and modulating the expression of GST-?.

SUBMITTER: Sun KX

PROVIDER: S-EPMC4667519 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Publications

MicroRNA-186 induces sensitivity of ovarian cancer cells to paclitaxel and cisplatin by targeting ABCB1.

Sun Kai-Xuan KX Jiao Jin-Wen JW Chen Shuo S Liu Bo-Liang BL Zhao Yang Y

Journal of ovarian research 20151202

<h4>Background</h4>Recent studies have shown that microRNAs may regulate the ABCB1 gene (ATP-binding cassette, sub-family B [MDR/TAP], member 1). Computational programs have predicted that the 3'-untranslated region (3'-UTR) of ABCB1 contains a potential miRNA-binding site for miR-186. Here, we investigated the role of miR-186 in sensitizing ovarian cancer cells to paclitaxel and cisplatin.<h4>Results</h4>Human ovarian carcinoma cell lines OVCAR3, A2780, A2780/DDP, and A2780/Taxol were exposed t ...[more]

PMID: 26626440

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Project description:Aquaporins (AQPs) are important mediators of water permeability and are closely associated with tumor cell proliferation, migration, angiogenesis and chemoresistance. Moreover, the chemosensitivity of tumor cells to cisplatin (CDDP) is potentially affected by osmotic pressure. The present study was undertaken to determine whether hyperosmosis regulates ovarian cancer cell sensitivity to CDDP in vitro and to explore whether this is associated with AQP expression. The hyperosmotic stress was induced by D-sorbitol. 3AO ovarian cancer cells were treated with different concentrations of hypertonic medium and/or CDDP for various times, followed by measuring the inhibition rate of cell proliferation using an MTT assay. In addition, AQP expression in response to osmotic pressure and/or CDDP was measured by reverse transcription-quantitative polymerase chain reaction and western blotting. Cell proliferation in response to hypertonic stress was also measured when AQP5 was knocked down by small interfering (si)RNA. 3AO cell proliferation was inhibited by hyperosmotic stress, while the expression of AQP5, but not that of AQP1, AQP3 or AQP9, was increased in a dose- and time-dependent manner in hypertonic sorbitol-containing medium. When AQP5 was silenced by siRNA, cells were susceptible to hypertonic stress. MTT analyses showed that the inhibition of cell proliferation by a low dose of CDDP increased significantly with exposure to a hyperosmotic stimulus, and this effect was reduced when a high dose of CDDP was used. AQP5 expression was induced by a low dose of CDDP, but was reduced by a high dose of CDDP. However, hyperosmosis enhanced AQP5 mRNA expression at every dose of CDDP tested, compared with isotonic medium. With prolonged treatment time, AQP5 expression was reduced by CDDP in hypertonic and isotonic culture medium. Thus, the effects of hyperosmosis on cell sensitivity to CDDP were associated with AQP5 expression. These results suggest that AQP5 expression in ovarian cancer cells is induced by hypertonic medium, and that the sensitivity of ovarian cancer cells to CDDP can be regulated by hyperosmosis associated with AQP5 expression.

Dataset Information

MicroRNA-186 induces sensitivity of ovarian cancer cells to paclitaxel and cisplatin by targeting ABCB1.

Background

Results

Conclusion

Publications

MicroRNA-186 induces sensitivity of ovarian cancer cells to paclitaxel and cisplatin by targeting ABCB1.

Similar Datasets

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