%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