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

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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.

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Acknowledgements

This work has been supported by the Chinese National Natural Science Foundation (grant no. 30800518 to Y. Chen) and the New Teachers of Doctor Fund Project of Ministry of Education (grant no. 200805331090 to Y. Chen).

Conflict of interest

All authors declared that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, Xiangya Hospital, Central South University, Changsha, 410008, China

    Furong Dai, Yi Zhang, Xin Zhu & Nianchun Shan

  2. Department of Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha, 410008, China

    Yuxiang Chen

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  1. Furong Dai
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  2. Yi Zhang
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  3. Xin Zhu
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  4. Nianchun Shan
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Correspondence to Yuxiang Chen.

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Dai, F., Zhang, Y., Zhu, X. et al. Anticancer role of MUC1 aptamer–miR-29b chimera in epithelial ovarian carcinoma cells through regulation of PTEN methylation. Targ Oncol 7, 217–225 (2012). https://doi.org/10.1007/s11523-012-0236-7

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  • DOI: https://doi.org/10.1007/s11523-012-0236-7

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