title: MicroRNA miR-214 regulates ovarian cancer cell stemness by targeting p53/Nanog.
abstract: Previous studies have shown aberrant expression of miR-214 in human malignancy. Elevated miR-214 is associated with chemoresistance and metastasis. In this study, we identified miR-214 regulation of ovarian cancer stem cell (OCSC) properties by targeting p53/Nanog axis. Enforcing expression of miR-214 increases, whereas knockdown of miR-214 decreases, OCSC population and self-renewal as well as the Nanog level preferentially in wild-type p53 cell lines. Furthermore, we found that p53 is directly repressed by miR-214 and that miR-214 regulates Nanog through p53. Expression of p53 abrogated miR-214-induced OCSC properties. These data suggest the critical role of miR-214 in OCSC via regulation of the p53-Nanog axis and miR-214 as a therapeutic target for ovarian cancer.
authors.affiliation: Department of Molecular Oncology, University of South Florida, Tampa, Florida.
authors.forename: Cheng-Xiong
authors.initials: CX
authors.lastname: Xu
authors.affiliation: Department of Molecular Oncology, University of South Florida, Tampa, Florida.
authors.forename: Meng
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Molecular Oncology, University of South Florida, Tampa, Florida.
authors.forename: Lei
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Molecular Oncology, University of South Florida, Tampa, Florida.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.affiliation: Cancer Epidemiology, University of South Florida, Tampa, Florida.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Permuth-Wey
authors.affiliation: Department of Pathology and Cell Biology, Morsani College of Medicine, University of South Florida, Tampa, Florida.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Kruk
authors.affiliation: Gynecologic Oncology, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, Florida.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Wenham
authors.affiliation: Department of Pathology and Cell Biology, Morsani College of Medicine, University of South Florida, Tampa, Florida; Gynecologic Oncology, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, Florida.
authors.forename: Santo V
authors.initials: SV
authors.lastname: Nicosia
authors.affiliation: Gynecologic Oncology, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, Florida.
authors.forename: Johnathan M
authors.initials: JM
authors.lastname: Lancaster
authors.affiliation: Cancer Epidemiology, University of South Florida, Tampa, Florida.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Sellers
authors.affiliation: Department of Molecular Oncology, University of South Florida, Tampa, Florida; Department of Pathology and Cell Biology, Morsani College of Medicine, University of South Florida, Tampa, Florida. Electronic address: jin.cheng@moffitt.org.
authors.forename: Jin Q
authors.initials: JQ
authors.lastname: Cheng
mesh_terms: D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D000071317:Nanog Homeobox Protein; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; C547397:MIRN214 microRNA, human; D035683:MicroRNAs; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D012334:RNA, Neoplasm; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53