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

被引：436

作者：

Zhang, Lin ^{[1
,3
]}

Volinia, Stefano ^{[7
,8
,9
]}

Bonome, Tomas ^{[10
]}

Calin, George Adrian ^{[7
,8
,9
]}

Greshock, Joel ^{[2
]}

Yang, Nuo ^{[1
]}

Liu, Chang-Gong ^{[7
,8
,9
]}

Giannakakis, Antonis ^{[1
,11
]}

Alexiou, Pangiotis ^{[12
]}

Hasegawa, Kosei ^{[1
]}

Johnstone, Cameron N. ^{[4
]}

Megraw, Molly S. ^{[5
]}

Adams, Sarah ^{[1
,3
]}

Lassus, Heini ^{[13
]}

Huang, Jia ^{[2
]}

Kaur, Sippy ^{[13
]}

Liang, Shun ^{[1
]}

Sethupathy, Praveen ^{[5
]}

Leminen, Arto ^{[13
]}

Simossis, Victor A. ^{[12
]}

Sandaltzopoulos, Raphael ^{[11
]}

Naomoto, Yoshio ^{[14
]}

Katsaros, Dionyssios ^{[15
]}

Gimotty, Phyllis A. ^{[6
]}

DeMichele, Angela ^{[4
]}

Huang, Qihong ^{[16
]}

Butzow, Ralf ^{[13
]}

Rustgi, Anil K. ^{[4
]}

Weber, Barbara L. ^{[2
]}

Birrer, Michael J. ^{[10
]}

Hatzigeorgiou, Artemis G. ^{[2
,5
,12
]}

Croce, Carlo M.

Coukos, George ^{[1
,2
,3
]}

机构：

[1] Univ Penn, Ctr Res Early Detect & Cure Ovarian Canc & Gyneco, Philadelphia, PA 19104 USA

[2] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA

[3] Univ Penn, Dept Obstet, Philadelphia, PA 19104 USA

[4] Univ Penn, Dept Med, Philadelphia, PA 19104 USA

[5] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA

[6] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA

[7] Ohio State Univ, Dept Mol Virol, Columbus, OH 43210 USA

[8] Ohio State Univ, Dept Immunol, Columbus, OH 43210 USA

[9] Ohio State Univ, Dept Med Genet, Columbus, OH 43210 USA

[10] NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20814 USA

[11] Democritus Univ Thrace, Lab Gene Express Modern Diag & Therapeut Methods, Alexandroupolis 68100, Greece

[12] Biomed Sci Res Ctr Alexander Fleming, Inst Mol Oncol, Varkiza 16672, Greece

[13] Univ Helsinki, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland

[14] Okayama Univ, Dept Surg Oncol, Okayama 7008530, Japan

[15] Univ Turin, Dept Obstet & Gynecol, I-10124 Turin, Italy

[16] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2008年 / 105卷 / 19期

关键词：

Dlk1-Gtl2; domain; noncoding RNA;

D O I：

10.1073/pnas.0801615105

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 epithelia[ 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 approximate to 15% and at least approximate to 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.

引用

页码：7004 / 7009

页数：6

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