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


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.

SUBMITTER: Zhang L 

PROVIDER: S-EPMC2383982 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

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

Zhang Lin L   Volinia Stefano S   Bonome Tomas T   Calin George Adrian GA   Greshock Joel J   Yang Nuo N   Liu Chang-Gong CG   Giannakakis Antonis A   Alexiou Pangiotis P   Hasegawa Kosei K   Johnstone Cameron N CN   Megraw Molly S MS   Adams Sarah S   Lassus Heini H   Huang Jia J   Kaur Sippy S   Liang Shun S   Sethupathy Praveen P   Leminen Arto A   Simossis Victor A VA   Sandaltzopoulos Raphael R   Naomoto Yoshio Y   Katsaros Dionyssios D   Gimotty Phyllis A PA   DeMichele Angela A   Huang Qihong Q   Bützow Ralf R   Rustgi Anil K AK   Weber Barbara L BL   Birrer Michael J MJ   Hatzigeorgiou Artemis G AG   Croce Carlo M CM   Coukos George G  

Proceedings of the National Academy of Sciences of the United States of America 20080505 19


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 hybridizat  ...[more]

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