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Tumor Biology

, Volume 35, Issue 12, pp 12369–12378 | Cite as

MicroRNA-449a reduces cell survival and enhances cisplatin-induced cytotoxicity via downregulation of NOTCH1 in ovarian cancer cells

  • Yanqi Zhou
  • Qiaoyun Chen
  • Rong Qin
  • Kaifeng Zhang
  • Hao Li
Research Article

Abstract

Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancies. Platinum-based chemotherapy is the first-line treatment for the advanced ovarian cancer, but resistance to cisplatin remains a major obstacle to successful treatment. MicroRNAs (miRNAs) are a class of non-coding RNAs that play important roles in disease processes, including the development of drug resistance. In this study, we found miR-449a were significantly downregulated in the cisplatin-resistant ovarian cell lines SKOV3/DDP and A2780/DDP, compared with their sensitive parent line SKOV3 and A2780, respectively. The overexpression of miR-449a increased cisplatin sensitivity of SKOV3/DDP and A2780/DDP cells by inhibiting proliferation and promoting apoptosis. The luciferase assay confirmed that miR-449a functioned through suppressing NOTCH1 directly. Concordantly, BALB/c nude mice that were injected intraperitoneally with SKOV3/DDP cells transfected with miR-449a mimics exhibited enhanced cisplatin sensitivity in vivo. Taken together, these results suggest that the ectopic expression of miR-449a may be a promising therapeutic strategy for the management of cisplatin resistance in ovarian cancer.

Keywords

Ovarian cancer MicroRNA-449a Cisplatin resistance NOTCH1 

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Yanqi Zhou
    • 1
  • Qiaoyun Chen
    • 1
  • Rong Qin
    • 2
  • Kaifeng Zhang
    • 1
  • Hao Li
    • 3
  1. 1.Department of Gynaecology and ObstetricsThe Affiliated People’s Hospital of Jiangsu UniversityZhenjiangChina
  2. 2.Department of OncologyThe Affiliated People’s Hospital of Jiangsu UniversityZhenjiangChina
  3. 3.Department of Clinical LaboratoryThe Taixing People’s HospitalTaixingChina

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