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MiR-218 regulates cisplatin chemosensitivity in breast cancer by targeting BRCA1

  • Research Article
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Tumor Biology

Abstract

Cisplatin resistance presents a major challenge in the successful treatment of breast cancer, and its mechanism has not been documented well. In this study, to determine the relationship between chemotherapy resistance and microRNA (miRNA) expression during the development of cisplatin resistance in breast cancer, we used microRNA microarrays analysis successfully identified 19 miRNAs that were either overexpressed or underexpressed (8 upregulated and 11 downregulated) in the MCF-7 cell line and its cisplatin-resistant variant MCF-7/DDP. Among them, the miR-218 was most downregulated in cisplatin-resistant cell lines and identified that breast cancer 1 (BRCA1) was the cellular targets of miR-218. In vivo assay also demonstrated that restoring miR-218 expression in MCF-7/DDP cell line could sensitize cells against cisplatin, thereby increasing cisplatin-mediated tumor cell apoptosis and reducing DNA repair. Kaplan–Meier survival analysis indicated that patients with breast cancer display high levels of miR-218 and low levels of BRCA1 expression; these patients may gain the greatest benefits in terms of increased survival when treated with cisplatin. All of these results indicated that miR-218 has a significant function in the development of cisplatin resistance in breast cancer. Restoring miR-218 expression may constitute a novel therapeutic approach by which to increase cisplatin sensitivity in breast cancer.

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Acknowledgments

This research was supported by grants from the National Natural Science Foundation of China (81172365).

Conflicts of interest

None

Author contributions

XH and XZ conceived and designed the experiments. XH, LD, XX, and NW performed the experiments. XH and ZZ analyzed the data. XH and HD contributed reagents/materials/analysis tools. XH and XZ wrote the paper.

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Authors and Affiliations

  1. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, People’s Republic of China

    Xiao He & Xiefu Zhang

  2. Second Department of Breast Surgery, Hunan Provincial Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410006, Hunan Province, People’s Republic of China

    Xiao He, Nengbin Wan, Zhengyu Zhou & Hongwu Deng

  3. Department of Internal Medicine, The Maternal and Child Heath Hospital of Hunan Province, Changsha, 410008, Hunan Province, People’s Republic of China

    Xia Xiao

  4. Cancer Research Institute, College of Medicine, University of South China, Hengyang, 421001, Hunan Province, People’s Republic of China

    Lin Dong

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  1. Xiao He
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  2. Xia Xiao
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  3. Lin Dong
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  4. Nengbin Wan
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  5. Zhengyu Zhou
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  7. Xiefu Zhang
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Correspondence to Xiefu Zhang.

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He, X., Xiao, X., Dong, L. et al. MiR-218 regulates cisplatin chemosensitivity in breast cancer by targeting BRCA1. Tumor Biol. 36, 2065–2075 (2015). https://doi.org/10.1007/s13277-014-2814-z

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  • DOI: https://doi.org/10.1007/s13277-014-2814-z

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