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

• DOI: 10.1007/s11523-012-0236-7
• Publication Date: 2012-11-19T08:40:01Z
• Authors: Furong Dai; Yi Zhang; Xin Zhu; Nianchun Shan; Yuxiang Chen
• Keywords: DNA (Cytosine-5-)-Methyltransferase 1; Ovarian Neoplasms; DNA Methyltransferase 3B; 0303 health sciences; Recombinant Fusion Proteins; Carcinoma; Mucin-1; PTEN Phosphohydrolase; Apoptosis; Aptamers, Nucleotide; DNA Methylation; Transfection; DNA Methyltransferase 3A; 3. Good health; MicroRNAs; 03 medical and health sciences; Gene Expression Regulation; Cell Line, Tumor; Humans; Female; DNA (Cytosine-5-)-Methyltransferases

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.