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Deregulation of miR-128 in Ovarian Cancer Promotes Cisplatin Resistance
  1. Bing Li, MD*,
  2. Hong Chen, MD,
  3. Nan Wu, MD*,
  4. Wen-Jing Zhang, MD* and
  5. Li-Xin Shang, MD*
  1. *Departments of Gynecology and Obstetrics, and
  2. Anesthesiology, the Military General Hospital of Beijing PLA, Beijng, China.
  1. Address correspondence and reprint requests to Li-Xin Shang, MD, Department of Gynecology and Obstetrics, the Military General Hospital of Beijing PLA, No. 5, Nanmencang, Dongcheng District, Beijing, 100700, China. E-mail: 601847608{at}qq.com.

Abstract

Objective Platinum-based chemotherapy is the standard treatment in advanced ovarian cancer, but most patients will relapse with drug-resistant disease. MicroRNAs have been demonstrated to function in chemoresistance in cancers. In this study, we focused on the role of miR-128 in cisplatin-resistant ovarian cancer.

Materials and Methods The expression of miR-128 RNA and its targeted genes, the polycomb ring finger oncogene Bmi-1 and ATP-binding cassette subfamily C member 5 (ABCC5), were investigated in the epithelial ovarian cancer cells and ovarian carcinomas.

Results miR-128 expression was significantly reduced in the cisplatin-resistant human epithelial ovarian cancer cell line SKOV3/CP compared with parental SKOV3 cells and decreased upon treatment with cisplatin in a concentration-dependent manner in SKOV3, OVCAR3, and PEO14 cells. Overexpression of miR-128 resensitized SKOV3/CP cells to cisplatin and reduced the expression of cisplatin-resistant–related proteins ABCC5 and Bmi-1, whereas miR-128 inhibitors increased cisplatin resistance in SKOV3 cells. Cisplatin combined with miR-128 agomirs inhibited the growth of SKOV3/CP xenograft tumors more effectively than cisplatin alone. Diminished expression of ABCC5 and Bmi-1 and higher cisplatin concentrations were observed in tumor tissue of mice treated with miR-128 agomirs in addition to cisplatin.

Conclusions Taken together, our findings suggest that miR-128 may act as a promising therapeutic target for improvement of tumor sensitivity to cisplatin.

  • miR-128
  • Cisplatin
  • Epithelial ovarian cancer
  • ABCC5
  • Bmi-1

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Footnotes

  • Drs. Bing Li and Hong Chen contributed equally to this study.

  • The authors declare no conflicts of interest.

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