title: Pluripotent factor lin-28 and its homologue lin-28b in epithelial ovarian cancer and their associations with disease outcomes and expression of let-7a and IGF-II.
abstract: Lin-28 and lin-28B are RNA-binding proteins which can block microRNA let-7 maturation and affect the differentiation and proliferation of embryonic stem cells. Lin-28 may also regulate the expression of insulin-like growth factor II (IGF-II). As one of the pluripotent factors involved in making induced pluripotent stem cells (iPS), lin-28 is considered a potential therapeutic target for cancer treatment. To further understand the role of lin-28 in cancer, we analysed the expression of lin-28 and its homologue lin-28B in tumour samples, and evaluated their associations with let-7a maturation, IGF-II expression, disease features and outcomes in 211 patients with primary epithelial ovarian cancer. The analysis showed that both lin-28 and lin-28B were positively correlated with primary and pre-let-7a-3; lin-28B, not lin-28, was inversely correlated with mature let-7a. A positive correlation was also observed between lin-28B and IGF-II expression, while no association was found between lin-28B and IGF-I or IGFBP-3. The study further demonstrated that lin-28B expression was associated with the risk of disease progression and death; patients with high lin-28B had shorter progression-free and overall survival than those with low lin-28B. These results seem to support the findings of recent in vitro experiments, showing that lin-28 blocks the process of let-7a maturation. Our study also suggests that lin-28B may promote ovarian cancer progression and serve as an unfavourable prognostic marker for the disease. The correlation between lin-28B and IGF-II indicates that the growth factor may mediate the effect of lin-28B on tumour growth.
authors.affiliation: Department of Epidemiology and Public Health, Yale Cancer Center, Yale University School of Medicine, 60 College Street, New Haven, CT 06520-8034, USA.
authors.forename: Lingeng
authors.initials: L
authors.lastname: Lu
authors.forename: Dionyssios
authors.initials: D
authors.lastname: Katsaros
authors.forename: Khvaramze
authors.initials: K
authors.lastname: Shaverdashvili
authors.forename: Biyun
authors.initials: B
authors.lastname: Qian
authors.forename: Yixing
authors.initials: Y
authors.lastname: Wu
authors.forename: Irene A Rigault
authors.initials: IA
authors.lastname: de la Longrais
authors.forename: Mario
authors.initials: M
authors.lastname: Preti
authors.forename: Guido
authors.initials: G
authors.lastname: Menato
authors.forename: Herbert
authors.initials: H
authors.lastname: Yu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: D004268:DNA-Binding Proteins; C516326:LIN28B protein, human; C000715187:Lin28A protein, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; C487931:mirnlet7 microRNA, human; D007335:Insulin-Like Growth Factor II