Targeted Oncology

, Volume 7, Issue 4, pp 217–225

Anticancer role of MUC1 aptamer–miR-29b chimera in epithelial ovarian carcinoma cells through regulation of PTEN methylation

  • Furong Dai
  • Yi Zhang
  • Xin Zhu
  • Nianchun Shan
  • Yuxiang Chen
Original Research

DOI: 10.1007/s11523-012-0236-7

Cite this article as:
Dai, F., Zhang, Y., Zhu, X. et al. Targ Oncol (2012) 7: 217. doi:10.1007/s11523-012-0236-7

Abstract

Ovarian cancer has a poor prognosis and advanced ovarian cancer lacks effective therapy. In this study, we seek to establish targeting therapy for ovarian cancer through tumor tissue-specific delivery of miRNA-29b to reexpress PTEN tumor-suppressor gene. A chimera (Chi-29b) was constructed to compose of a mucin 1 (MUC1) aptamer targeting tumor cell surface MUC1 protein and miR-29b inhibiting DNA methyltransferases’ expression, subsequently reexpressing PTEN gene. The specificity and efficacy of the chimera delivery were analyzed in OVCAR-3 ovarian tumor cells, and the biological activities of the chimera were identified by the expression of its downstream molecules and cell apoptosis. We demonstrated that Chi-29b chimera can be specifically delivered into OVCAR-3 cells in a concentration-dependent manner. Dicer efficiently cleaved the Chi-29b chimera to release miR-29b. Chi-29b chimera downregulated Dnmt1, Dnmt3a, and Dnmt3b protein levels; induced hypomethylation in PTEN promoter; and upregulated PTEN mRNA and protein expression in OVCAR-3 cells. Importantly, Chi-29b chimera significantly induced apoptosis in OVCAR-3 cells. Our study indicated that Chi-29b chimera can effectively exert antitumor effect through specific delivery of miR-29b into OVCAR-3 tumor cells, subsequently reexpressing PTEN gene and inducing cell apoptosis.

Keywords

Ovarian cancer Aptamer miRNA Chimera PTEN Methylation 

Copyright information

© Springer-Verlag France 2012

Authors and Affiliations

  • Furong Dai
    • 1
  • Yi Zhang
    • 1
  • Xin Zhu
    • 1
  • Nianchun Shan
    • 1
  • Yuxiang Chen
    • 2
  1. 1.Department of Obstetrics and Gynaecology, Xiangya HospitalCentral South UniversityChangshaChina
  2. 2.Department of Hepatobiliary and Enteric Surgery Research Center, Xiangya HospitalCentral South UniversityChangshaChina

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