%0 Journal Article %J Proc Natl Acad Sci U S A %D 2008 %T Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer. %A Zhang, Lin %A Volinia, Stefano %A Bonome, Tomas %A Calin, George Adrian %A Greshock, Joel %A Yang, Nuo %A Liu, Chang-Gong %A Giannakakis, Antonis %A Alexiou, Pangiotis %A Hasegawa, Kosei %A Johnstone, Cameron N %A Megraw, Molly S %A Adams, Sarah %A Lassus, Heini %A Huang, Jia %A Kaur, Sippy %A Liang, Shun %A Sethupathy, Praveen %A Leminen, Arto %A Simossis, Victor A %A Sandaltzopoulos, Raphael %A Naomoto, Yoshio %A Katsaros, Dionyssios %A Gimotty, Phyllis A %A DeMichele, Angela %A Huang, Qihong %A Bützow, Ralf %A Rustgi, Anil K %A Weber, Barbara L %A Birrer, Michael J %A Hatzigeorgiou, Artemis G %A Croce, Carlo M %A Coukos, George %K DNA, Neoplasm %K Down-Regulation %K Epigenesis, Genetic %K Epithelial Cells %K Female %K Gene Expression Profiling %K Gene Expression Regulation, Neoplastic %K Genome, Human %K Humans %K MicroRNAs %K Neoplasm Staging %K Ovarian Neoplasms %K Ribonuclease III %K RNA, Messenger %K Survival Analysis %X

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.

%B Proc Natl Acad Sci U S A %V 105 %P 7004-9 %8 2008 May 13 %G eng %N 19 %R 10.1073/pnas.0801615105 %0 Journal Article %J Nucleic Acids Res %D 2007 %T miRGen: a database for the study of animal microRNA genomic organization and function. %A Megraw, Molly %A Sethupathy, Praveen %A Corda, Benoit %A Hatzigeorgiou, Artemis G %K Animals %K Data Interpretation, Statistical %K Databases, Nucleic Acid %K Genomics %K Humans %K Internet %K Mice %K MicroRNAs %K Rats %K User-Computer Interface %X

miRGen is an integrated database of (i) positional relationships between animal miRNAs and genomic annotation sets and (ii) animal miRNA targets according to combinations of widely used target prediction programs. A major goal of the database is the study of the relationship between miRNA genomic organization and miRNA function. This is made possible by three integrated and user friendly interfaces. The Genomics interface allows the user to explore where whole-genome collections of miRNAs are located with respect to UCSC genome browser annotation sets such as Known Genes, Refseq Genes, Genscan predicted genes, CpG islands and pseudogenes. These miRNAs are connected through the Targets interface to their experimentally supported target genes from TarBase, as well as computationally predicted target genes from optimized intersections and unions of several widely used mammalian target prediction programs. Finally, the Clusters interface provides predicted miRNA clusters at any given inter-miRNA distance and provides specific functional information on the targets of miRNAs within each cluster. All of these unique features of miRGen are designed to facilitate investigations into miRNA genomic organization, co-transcription and targeting. miRGen can be freely accessed at http://www.diana.pcbi.upenn.edu/miRGen.

%B Nucleic Acids Res %V 35 %P D149-55 %8 2007 Jan %G eng %N Database issue %R 10.1093/nar/gkl904 %0 Journal Article %J Nat Methods %D 2006 %T A guide through present computational approaches for the identification of mammalian microRNA targets. %A Sethupathy, Praveen %A Megraw, Molly %A Hatzigeorgiou, Artemis G %K 3' Untranslated Regions %K 5' Untranslated Regions %K Animals %K Computational Biology %K Gene Targeting %K Humans %K MicroRNAs %K Predictive Value of Tests %K RNA, Messenger %K Sensitivity and Specificity %K Software %X

Computational microRNA (miRNA) target prediction is a field in flux. Here we present a guide through five widely used mammalian target prediction programs. We include an analysis of the performance of these individual programs and of various combinations of these programs. For this analysis we compiled several benchmark data sets of experimentally supported miRNA-target gene interactions. Based on the results, we provide a discussion on the status of target prediction and also suggest a stepwise approach toward predicting and selecting miRNA targets for experimental testing.

%B Nat Methods %V 3 %P 881-6 %8 2006 Nov %G eng %N 11 %R 10.1038/nmeth954