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MicroRNA-873 mediates multidrug resistance in ovarian cancer cells by targeting ABCB1

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Tumor Biology

Abstract

Ovarian cancer is commonly treated with cisplatin and paclitaxel combination chemotherapy; however, ovarian cancer cells often develop resistance to these drugs. Increasingly, microRNAs (miRNAs) including miR-873 have been implicated in drug resistance in many cancers, but the role of miR-873 in ovarian cancer remains unknown. MTT cell viability assays revealed that the sensitivities of ovarian cancer lines to cisplatin and paclitaxel increased following transfection with miR-873 (P < 0.05). After predicting the miR-873 binding region in the 3′-untranslated region of ABCB1, dual-luciferase reporter assay confirmed this prediction. RT-PCR and Western blotting revealed that MDR1 expression was significantly downregulated after transfection with miR-873 and upregulated after transfection with anti-miR-873 at both mRNA and protein levels compared to negative controls (P < 0.05). Experiments in a mouse xenograft model confirmed that intratumoral administration of miR-873 could enhance the efficacy of cisplatin in inhibiting tumor growth in ovarian cancer in vivo (P < 0.05). ABCB1 overexpression reduced sensitivities of ovarian cancer lines OVCAR3 and A2780 to cisplatin and paclitaxel, which can be reversed by miR-873 mimic transfection (P < 0.05). In summary, we demonstrated that overexpression of miR-873 increased the sensitivity of ovarian cancer cells to cisplatin and paclitaxel by targeting MDR1 expression. Our findings suggest that combination therapies with chemotherapy agents and miR-873 may suppress drug resistance in ovarian cancer.

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Acknowledgements

This work was supported by Liaoning Science and Technology Grant (2013021077) and the Natural Scientific Foundation of China (No. 81472502).

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang, 110013, China

    Di-di Wu, Xue-song Li, Xiao-Na Meng, Jing Yan & Zhi-hong Zong

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  1. Di-di Wu
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  2. Xue-song Li
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Correspondence to Zhi-hong Zong.

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Authors’ contributions

Z-H Z conceived the study and analyzed interpretation. D-D W, X-S L, X-N M, and JY carried out the experiments and analyzed the data. Z-H Z wrote the first and final draft of the manuscript. All authors read and approved the final manuscript.

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Supplementary Table 1

Primers for RT-PCR. (DOC 31 kb)

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Wu, Dd., Li, Xs., Meng, XN. et al. MicroRNA-873 mediates multidrug resistance in ovarian cancer cells by targeting ABCB1. Tumor Biol. 37, 10499–10506 (2016). https://doi.org/10.1007/s13277-016-4944-y

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  • DOI: https://doi.org/10.1007/s13277-016-4944-y

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