title: MicroRNA-449a reduces cell survival and enhances cisplatin-induced cytotoxicity via downregulation of NOTCH1 in ovarian cancer cells.
abstract: Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancies. Platinum-based chemotherapy is the first-line treatment for the advanced ovarian cancer, but resistance to cisplatin remains a major obstacle to successful treatment. MicroRNAs (miRNAs) are a class of non-coding RNAs that play important roles in disease processes, including the development of drug resistance. In this study, we found miR-449a were significantly downregulated in the cisplatin-resistant ovarian cell lines SKOV3/DDP and A2780/DDP, compared with their sensitive parent line SKOV3 and A2780, respectively. The overexpression of miR-449a increased cisplatin sensitivity of SKOV3/DDP and A2780/DDP cells by inhibiting proliferation and promoting apoptosis. The luciferase assay confirmed that miR-449a functioned through suppressing NOTCH1 directly. Concordantly, BALB/c nude mice that were injected intraperitoneally with SKOV3/DDP cells transfected with miR-449a mimics exhibited enhanced cisplatin sensitivity in vivo. Taken together, these results suggest that the ectopic expression of miR-449a may be a promising therapeutic strategy for the management of cisplatin resistance in ovarian cancer.
authors.affiliation: Department of Gynaecology and Obstetrics, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212002, Jiangsu, China.
authors.forename: Yanqi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Qiaoyun
authors.initials: Q
authors.lastname: Chen
authors.forename: Rong
authors.initials: R
authors.lastname: Qin
authors.forename: Kaifeng
authors.initials: K
authors.lastname: Zhang
authors.forename: Hao
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology; D004195:Disease Models, Animal; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D034622:RNA Interference; D051881:Receptor, Notch1 / Q000737:chemistry / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: C544530:MIRN449 microRNA, human; D035683:MicroRNAs; D051881:Receptor, Notch1; D002945:Cisplatin