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-π, 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-π 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-π 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-π.

journal_name

J Ovarian Res

authors

Sun KX,Jiao JW,Chen S,Liu BL,Zhao Y

doi

10.1186/s13048-015-0207-6

subject

Has Abstract

pub_date

2015-12-02 00:00:00

pages

80

issn

1757-2215

pii

10.1186/s13048-015-0207-6

journal_volume

8

pub_type

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