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

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

doi:10.1073/pnas.0801615105

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.

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Titolo:	Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer
Autori:	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 mostra contributor esterni nascondi contributor esterni
Data di pubblicazione:	2008
Rivista:	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Handle:	http://hdl.handle.net/11392/2357507
Appare nelle tipologie:	03.1 Articolo su rivista

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