title: MicroRNA signatures in human ovarian cancer.
abstract: Epithelial ovarian cancer (EOC) is the sixth most common cancer in women worldwide and, despite advances in detection and therapies, it still represents the most lethal gynecologic malignancy in the industrialized countries. Unfortunately, still relatively little is known about the molecular events that lead to the development of this highly aggressive disease. The relatively recent discovery of microRNAs (miRNA), a class of small noncoding RNAs targeting multiple mRNAs and triggering translation repression and/or RNA degradation, has revealed the existence of a new level of gene expression regulation. Multiple studies involving various types of human cancers proved that miRNAs have a causal role in tumorigenesis. Here we show that, in comparison to normal ovary, miRNAs are aberrantly expressed in human ovarian cancer. The overall miRNA expression could clearly separate normal versus cancer tissues. The most significantly overexpressed miRNAs were miR-200a, miR-141, miR-200c, and miR-200b, whereas miR-199a, miR-140, miR-145, and miR-125b1 were among the most down-modulated miRNAs. We could also identify miRNAs whose expression was correlated with specific ovarian cancer biopathologic features, such as histotype, lymphovascular and organ invasion, and involvement of ovarian surface. Moreover, the levels of miR-21, miR-203, and miR-205, up-modulated in ovarian carcinomas compared with normal tissues, were significantly increased after 5-aza-2'-deoxycytidine demethylating treatment of OVCAR3 cells, suggesting that the DNA hypomethylation could be the mechanism responsible for their overexpression. Our results indicate that miRNAs might play a role in the pathogenesis of human EOC and identify altered miRNA gene methylation as a possible epigenetic mechanism involved in their aberrant expression.
authors: Molecular Biology Unit, Department of Experimental Oncology, Fondazione Istituti di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale Tumori, Milano, Italy.
authors: Marilena V
authors: MV
authors: Iorio
authors: Rosa
authors: R
authors: Visone
authors: Gianpiero
authors: G
authors: Di Leva
authors: Valentina
authors: V
authors: Donati
authors: Fabio
authors: F
authors: Petrocca
authors: Patrizia
authors: P
authors: Casalini
authors: Cristian
authors: C
authors: Taccioli
authors: Stefano
authors: S
authors: Volinia
authors: Chang-Gong
authors: CG
authors: Liu
authors: Hansjuerg
authors: H
authors: Alder
authors: George A
authors: GA
authors: Calin
authors: Sylvie
authors: S
authors: Ménard
authors: Carlo M
authors: CM
authors: Croce
mesh_terms: D045744:Cell Line, Tumor; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm; D035683:MicroRNAs