title: Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer.
abstract: MicroRNAs (miRNAs) are an abundant class of small noncoding RNAs that function as negative gene regulators. miRNA deregulation is involved in the initiation and progression of human cancer; however, the underlying mechanism and its contributions to genome-wide transcriptional changes in cancer are still largely unknown. We studied miRNA deregulation in human epithelial ovarian cancer by integrative genomic approach, including miRNA microarray (n = 106), array-based comparative genomic hybridization (n = 109), cDNA microarray (n = 76), and tissue array (n = 504). miRNA expression is markedly down-regulated in malignant transformation and tumor progression. Genomic copy number loss and epigenetic silencing, respectively, may account for the down-regulation of approximately 15% and at least approximately 36% of miRNAs in advanced ovarian tumors and miRNA down-regulation contributes to a genome-wide transcriptional deregulation. Last, eight miRNAs located in the chromosome 14 miRNA cluster (Dlk1-Gtl2 domain) were identified as potential tumor suppressor genes. Therefore, our results suggest that miRNAs may offer new biomarkers and therapeutic targets in epithelial ovarian cancer.
authors.affiliation: Center for Research on Early Detection and Cure of Ovarian Cancer and Gynecology, Department of Obstetrics, University of Pennsylvania, Philadelphia, PA 19104, USA. linzhang@mail.med.upenn.edu
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Stefano
authors.initials: S
authors.lastname: Volinia
authors.forename: Tomas
authors.initials: T
authors.lastname: Bonome
authors.forename: George Adrian
authors.initials: GA
authors.lastname: Calin
authors.forename: Joel
authors.initials: J
authors.lastname: Greshock
authors.forename: Nuo
authors.initials: N
authors.lastname: Yang
authors.forename: Chang-Gong
authors.initials: CG
authors.lastname: Liu
authors.forename: Antonis
authors.initials: A
authors.lastname: Giannakakis
authors.forename: Pangiotis
authors.initials: P
authors.lastname: Alexiou
authors.forename: Kosei
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Cameron N
authors.initials: CN
authors.lastname: Johnstone
authors.forename: Molly S
authors.initials: MS
authors.lastname: Megraw
authors.forename: Sarah
authors.initials: S
authors.lastname: Adams
authors.forename: Heini
authors.initials: H
authors.lastname: Lassus
authors.forename: Jia
authors.initials: J
authors.lastname: Huang
authors.forename: Sippy
authors.initials: S
authors.lastname: Kaur
authors.forename: Shun
authors.initials: S
authors.lastname: Liang
authors.forename: Praveen
authors.initials: P
authors.lastname: Sethupathy
authors.forename: Arto
authors.initials: A
authors.lastname: Leminen
authors.forename: Victor A
authors.initials: VA
authors.lastname: Simossis
authors.forename: Raphael
authors.initials: R
authors.lastname: Sandaltzopoulos
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Naomoto
authors.forename: Dionyssios
authors.initials: D
authors.lastname: Katsaros
authors.forename: Phyllis A
authors.initials: PA
authors.lastname: Gimotty
authors.forename: Angela
authors.initials: A
authors.lastname: DeMichele
authors.forename: Qihong
authors.initials: Q
authors.lastname: Huang
authors.forename: Ralf
authors.initials: R
authors.lastname: Bützow
authors.forename: Anil K
authors.initials: AK
authors.lastname: Rustgi
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Weber
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Birrer
authors.forename: Artemis G
authors.initials: AG
authors.lastname: Hatzigeorgiou
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
authors.forename: George
authors.initials: G
authors.lastname: Coukos
mesh_terms: D004273:DNA, Neoplasm; D015536:Down-Regulation / Q000235:genetics; D044127:Epigenesis, Genetic; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043244:Ribonuclease III / Q000235:genetics; D016019:Survival Analysis
chemical_list: D004273:DNA, Neoplasm; D035683:MicroRNAs; D012333:RNA, Messenger; C517918:DROSHA protein, human; D043244:Ribonuclease III