A MicroRNA Expression Signature for Cervical Cancer Prognosis

被引:257
作者
Hu, Xiaoxia [1 ]
Schwarz, Julie K. [1 ]
Lewis, James S., Jr. [2 ]
Huettner, Phyllis C. [2 ]
Rader, Janet S. [3 ]
Deasy, Joseph O. [1 ]
Grigsby, Perry W. [1 ,3 ]
Wang, Xiaowei [1 ]
机构
[1] Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
[3] Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA
关键词
MESENCHYMAL TRANSITION; MIR-200; FAMILY; TARGET PREDICTION; REPRESSORS ZEB1; CELLS; IDENTIFICATION; DELIVERY; GROWTH; GENES; SITES;
D O I
10.1158/0008-5472.CAN-09-3289
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Invasive cervical cancer is a leading cause of cancer death in women worldwide, resulting in about 300,000 deaths each year. The clinical outcomes of cervical cancer vary significantly and are difficult to predict. Thus, a method to reliably predict disease outcome would be important for individualized therapy by identifying patients with high risk of treatment failures before therapy. In this study, we have identified a microRNA (miRNA)-based signature for the prediction of cervical cancer survival. miRNAs are a newly identified family of small noncoding RNAs that are extensively involved in human cancers. Using an established PCR-based miRNA assay to analyze 102 cervical cancer samples, we identified miR-200a and miR-9 as two miRNAs that could predict patient survival. A logistic regression model was developed based on these two miRNAs and the prognostic value of the model was subsequently validated with independent cervical cancers. Further-more, functional studies were done to characterize the effect of miRNAs in cervical cancer cells. Our results suggest that both miR-200a and miR-9 could play important regulatory roles in cervical cancer control. In particular, miR-200a is likely to affect the metastatic potential of cervical cancer cells by coordinate suppression of multiple genes controlling cell motility. Cancer Res; 70(4); 1441-8. (C) 2010 AACR.
引用
收藏
页码:1441 / 1448
页数:8
相关论文
共 32 条
[1]   The functions of animal microRNAs [J].
Ambros, V .
NATURE, 2004, 431 (7006) :350-355
[2]   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
[3]   MicroRNA signatures in human cancers [J].
Calin, George A. ;
Croce, Carlo M. .
NATURE REVIEWS CANCER, 2006, 6 (11) :857-866
[4]   Transforming growth factor-β1, transforming growth factor-β2, and transforming growth factor-β3 enhance ovarian cancer metastatic potential by inducing a smad3-dependent epithelial-to-mesenchymal transition [J].
Do, Thuy-Vy ;
Kubba, Lena A. ;
Du, Hongyan ;
Sturgis, Charles D. ;
Woodruff, Teresa K. .
MOLECULAR CANCER RESEARCH, 2008, 6 (05) :695-705
[5]   The mir-200 family and mir-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1 [J].
Gregory, Philip A. ;
Bert, Andrew G. ;
Paterson, Emily L. ;
Barry, Simon C. ;
Tsykin, Anna ;
Farshid, Gelareh ;
Vadas, Mathew A. ;
Khew-Goodall, Yeesim ;
Goodall, Gregory J. .
NATURE CELL BIOLOGY, 2008, 10 (05) :593-601
[6]   Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation [J].
Heiden, Matthew G. Vander ;
Cantley, Lewis C. ;
Thompson, Craig B. .
SCIENCE, 2009, 324 (5930) :1029-1033
[7]   miRNA profiling for diagnosis and prognosis of human cancer [J].
Jay, Chris ;
Nemunaitis, John ;
Chen, Patrick ;
Fulgham, Pat ;
Tong, Alex W. .
DNA AND CELL BIOLOGY, 2007, 26 (05) :293-300
[8]   The let-7 MicroRNA represses cell proliferation pathways in human cells [J].
Johnson, Charles D. ;
Esquela-Kerscher, Aurora ;
Stefani, Giovanni ;
Byrom, Nlike ;
Kelnar, Kevin ;
Ovcharenko, Dmitriy ;
Wilson, Mike ;
Wang, Xiaowei ;
Shelton, Jeffrey ;
Shingara, Jaclyn ;
Chin, Lena ;
Brown, David ;
Slack, Frank J. .
CANCER RESEARCH, 2007, 67 (16) :7713-7722
[9]   A small piece in the cancer puzzle: microRNAs as tumor suppressors and oncogenes [J].
Kent, O. A. ;
Mendell, J. T. .
ONCOGENE, 2006, 25 (46) :6188-6196
[10]   The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2 [J].
Korpal, Manav ;
Lee, Esther S. ;
Hu, Guohong ;
Kang, Yibin .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (22) :14910-14914