| Literature DB >> 18458333 |
Lin Zhang1, Stefano Volinia, Tomas Bonome, George Adrian Calin, Joel Greshock, Nuo Yang, Chang-Gong Liu, Antonis Giannakakis, Pangiotis Alexiou, Kosei Hasegawa, Cameron N Johnstone, Molly S Megraw, Sarah Adams, Heini Lassus, Jia Huang, Sippy Kaur, Shun Liang, Praveen Sethupathy, Arto Leminen, Victor A Simossis, Raphael Sandaltzopoulos, Yoshio Naomoto, Dionyssios Katsaros, Phyllis A Gimotty, Angela DeMichele, Qihong Huang, Ralf Bützow, Anil K Rustgi, Barbara L Weber, Michael J Birrer, Artemis G Hatzigeorgiou, Carlo M Croce, George Coukos.
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.Entities:
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Year: 2008 PMID： 18458333 PMCID： PMC2383982 DOI： 10.1073/pnas.0801615105
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205