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

  • Research Article
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Tumor Biology

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.

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Authors and Affiliations

  1. Department of Gynaecology and Obstetrics, The Affiliated People’s Hospital of Jiangsu University, Zhenjiang, 212002, Jiangsu, China

    Yanqi Zhou, Qiaoyun Chen & Kaifeng Zhang

  2. Department of Oncology, The Affiliated People’s Hospital of Jiangsu University, Zhenjiang, 212002, Jiangsu, China

    Rong Qin

  3. Department of Clinical Laboratory, The Taixing People’s Hospital, Taixing, 225400, Jiangsu, China

    Hao Li

Authors
  1. Yanqi Zhou
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  2. Qiaoyun Chen
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  3. Rong Qin
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  4. Kaifeng Zhang
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  5. Hao Li
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Correspondence to Hao Li.

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Yanqi Zhou and Qiaoyun Chen contributed equally to this article and should be considered co-first authors.

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Zhou, Y., Chen, Q., Qin, R. et al. MicroRNA-449a reduces cell survival and enhances cisplatin-induced cytotoxicity via downregulation of NOTCH1 in ovarian cancer cells. Tumor Biol. 35, 12369–12378 (2014). https://doi.org/10.1007/s13277-014-2551-3

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  • DOI: https://doi.org/10.1007/s13277-014-2551-3

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