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 downregulation of ≈15% and at least ≈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. © 2008 by The National Academy of Sciences of the USA.

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

VOLINIA, Stefano;CROCE, Carlo Maria;
2008

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 downregulation of ≈15% and at least ≈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. © 2008 by The National Academy of Sciences of the USA.
Zhang, Lin; Volinia, Stefano; Bonome, Tomas; Calin, George Adrian; Greshock, Joel; Yang, Nuo; Liu, Chang Gong; Giannakakis, Antonis; Alexiou, Pangiotis; Hasegawa, Kosei; Johnstone, Cameron N.; Megraw, Molly S.; Adams, Sarah; Lassus, Heini; Huang, Jia; Kaur, Sippy; Liang, Shun; Sethupathy, Praveen; Leminen, Arto; Simossis, Victor A.; Sandaltzopoulos, Raphael; Naomoto, Yoshio; Katsaros, Dionyssios; Gimotty, Phyllis A.; Demichele, Angela; Huang, Qihong; Bützow, Ralf; Rustgi, Anil K.; Weber, Barbara L.; Birrer, Michael J.; Hatzigeorgiou, Artemis G.; Croce, Carlo Maria; Coukos, George
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2357507
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