title: Anticancer role of MUC1 aptamer-miR-29b chimera in epithelial ovarian carcinoma cells through regulation of PTEN methylation.
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.
authors.affiliation: Department of Obstetrics and Gynaecology, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Furong
authors.initials: F
authors.lastname: Dai
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Zhu
authors.forename: Nianchun
authors.initials: N
authors.lastname: Shan
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Chen
mesh_terms: D017209:Apoptosis; D052157:Aptamers, Nucleotide / Q000235:genetics*; D002277:Carcinoma / Q000628:therapy*; D045744:Cell Line, Tumor; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D018396:Mucin-1 / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000628:therapy*; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D014162:Transfection; D000097584:DNA Methyltransferase 3B
chemical_list: D052157:Aptamers, Nucleotide; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D035683:MicroRNAs; D018396:Mucin-1; D051059:PTEN Phosphohydrolase; D011993:Recombinant Fusion Proteins; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human; C532045:MIRN29a microRNA, human; C000619380:DNMT1 protein, human; C494929:PTEN protein, human