Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer.

TitleGenomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer.
Publication TypeJournal Article
Year of Publication2008
AuthorsZhang, 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
JournalProc Natl Acad Sci U S A
Date Published2008 May 13
KeywordsDNA, 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 JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID18458333
PubMed Central IDPMC2383982
Grant ListP01-CA83638 / CA / NCI NIH HHS / United States
R01-DK056645 / DK / NIDDK NIH HHS / United States