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

被引：439

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

共 49 条

[1] The functions of animal microRNAs [J].

Ambros, V .

NATURE, 2004, 431 (7006) :350-355

[2] MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].

Bartel, David P. .

CELL, 2007, 131 (04) :11-29

[3] p53-mediated activation of miRNA34 candidate tumor-suppressor genes [J].

Bommer, Guido T. ;

Gerin, Isabelle ;

Feng, Ying ;

Kaczorowski, Andrew J. ;

Kuick, Rork ;

Love, Robert E. ;

Zhai, Yali ;

Giordano, Thomas J. ;

Qin, Zhaohui S. ;

Moore, Bethany B. ;

MacDougald, Ormond A. ;

Cho, Kathleen R. ;

Fearon, Eric R. .

CURRENT BIOLOGY, 2007, 17 (15) :1298-1307

[4] Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia [J].

Calin, GA ;

Dumitru, CD ;

Shimizu, M ;

Bichi, R ;

Zupo, S ;

Noch, E ;

Aldler, H ;

Rattan, S ;

Keating, M ;

Rai, K ;

Rassenti, L ;

Kipps, T ;

Negrini, M ;

Bullrich, F ;

Croce, CM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (24) :15524-15529

[5] Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers [J].

Calin, GA ;

Sevignani, C ;

Dan Dumitru, C ;

Hyslop, T ;

Noch, E ;

Yendamuri, S ;

Shimizu, M ;

Rattan, S ;

Bullrich, F ;

Negrini, M ;

Croce, CM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (09) :2999-3004

[6] A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia [J].

Calin, GA ;

Ferracin, M ;

Cimmino, A ;

Di Leva, G ;

Shimizu, M ;

Wojcik, SE ;

Iorio, MV ;

Visone, R ;

Sever, NI ;

Fabbri, M ;

Iuliano, R ;

Palumbo, T ;

Pichiorri, F ;

Roldo, C ;

Garzon, R ;

Sevignani, C ;

Rassenti, L ;

Alder, H ;

Volinia, S ;

Liu, CG ;

Kipps, TJ ;

Negrini, M ;

Croce, CM .

NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (17) :1793-1801

[7] MicroRNA signatures in human cancers [J].

Calin, George A. ;

Croce, Carlo M. .

NATURE REVIEWS CANCER, 2006, 6 (11) :857-866

[8] MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells [J].

Chan, JA ;

Krichevsky, AM ;

Kosik, KS .

CANCER RESEARCH, 2005, 65 (14) :6029-6033

[9] Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis [J].

Chang, Tsung-Cheng ;

Wentzel, Erik A. ;

Kent, Oliver A. ;

Ramachandran, Kalyani ;

Mullendore, Michael ;

Lee, Kwang Hyuck ;

Feldmann, Georg ;

Yamakuchi, Munekazu ;

Ferlito, Marcella ;

Lowenstein, Charles J. ;

Arking, Dan E. ;

Beer, Michael A. ;

Maitra, Anirban ;

Mendell, Joshua T. .

MOLECULAR CELL, 2007, 26 (05) :745-752

[10] Overexpression of Dicer in precursor lesions of lung adenocarcinoma [J].

Chiosea, Simion ;

Jelezcova, Elena ;

Chandran, Uma ;

Luo, Jianhua ;

Mantha, Geeta ;

Sobol, Robert W. ;

Dacic, Sanja .

CANCER RESEARCH, 2007, 67 (05) :2345-2350

← 1 2 3 4 5 →