Tumor Biology

, Volume 36, Issue 3, pp 2065–2075 | Cite as

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

  • Xiao He
  • Xia Xiao
  • Lin Dong
  • Nengbin Wan
  • Zhengyu Zhou
  • Hongwu Deng
  • Xiefu Zhang
Research Article

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.

Keywords

MicroRNA Breast cancer Drug resistance Cisplatin BRCA1 

Notes

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.

Supplementary material

13277_2014_2814_MOESM1_ESM.pdf (20 kb)
ESM 1 (PDF 19 kb)
13277_2014_2814_MOESM2_ESM.pdf (445 kb)
ESM 2 (PDF 444 kb)
13277_2014_2814_MOESM3_ESM.doc (152 kb)
ESM 3 (DOC 152 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Xiao He
    • 1
    • 2
  • Xia Xiao
    • 3
  • Lin Dong
    • 4
  • Nengbin Wan
    • 2
  • Zhengyu Zhou
    • 2
  • Hongwu Deng
    • 2
  • Xiefu Zhang
    • 1
  1. 1.Department of Gastrointestinal SurgeryThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouPeople’s Republic of China
  2. 2.Second Department of Breast Surgery, Hunan Provincial Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaPeople’s Republic of China
  3. 3.Department of Internal MedicineThe Maternal and Child Heath Hospital of Hunan ProvinceChangshaPeople’s Republic of China
  4. 4.Cancer Research Institute, College of MedicineUniversity of South ChinaHengyangPeople’s Republic of China

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