|Title||Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer.|
|Publication Type||Journal Article|
|Year of Publication||2008|
|Authors||Zhang, L, Volinia, S, Bonome, T, Calin, GAdrian, Greshock, J, Yang, N, Liu, C-G, Giannakakis, A, Alexiou, P, Hasegawa, K, Johnstone, CN, Megraw, MS, Adams, S, Lassus, H, Huang, J, Kaur, S, Liang, S, Sethupathy, P, Leminen, A, Simossis, VA, Sandaltzopoulos, R, Naomoto, Y, Katsaros, D, Gimotty, PA, DeMichele, A, Huang, Q, Bützow, R, Rustgi, AK, Weber, BL, Birrer, MJ, Hatzigeorgiou, AG, Croce, CM, Coukos, G|
|Journal||Proc Natl Acad Sci U S A|
|Date Published||2008 May 13|
|Keywords||DNA, Neoplasm, Down-Regulation, Epigenesis, Genetic, Epithelial Cells, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genome, Human, Humans, MicroRNAs, Neoplasm Staging, Ovarian Neoplasms, Ribonuclease III, RNA, Messenger, Survival Analysis|
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.
|Alternate Journal||Proc. Natl. Acad. Sci. U.S.A.|
|PubMed Central ID||PMC2383982|
|Grant List||P01-CA83638 / CA / NCI NIH HHS / United States |
R01-DK056645 / DK / NIDDK NIH HHS / United States
Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer.
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