A microRNA expression signature of human solid tumors defines cancer gene targets

Proceedings of the National Academy of Sciences of the United States of America - Tập 103 Số 7 - Trang 2257-2261 - 2006
Stefano Volinia1,2, George A. Calin3, Chang-Gong Liu3, Stefan Ambs4, Amelia Cimmino3, Fabio Petrocca3, Rosa Visone3, Marilena V. Iorio3, Claudia Roldo3, Manuela Ferracin5, Robyn L. Prueitt4, Nozumu Yanaihara4, Giovanni Lanza5, Aldo Scarpa6, Andrea Vecchione7, Massimo Negrini5, Curtis C. Harris4, Carlo M. Croce3
1Department of Molecular Virology, Immunology, and Medical Genetics and Cancer Comprehensive Center, Ohio State University, Columbus, OH 43210, USA.
2Telethon Facility–Data Mining for Analysis of DNA Microarrays, Department of Morphology and Embryology, and
3*Department of Molecular Virology, Immunology, and Medical Genetics and Cancer Comprehensive Center, Ohio State University, Columbus, OH 43210;
4Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
5Department of Experimental and Diagnostic Medicine and Interdepartmental Center for Cancer Research, University of Ferrara, 44100 Ferrara, Italy;
6Department of Pathology, University of Verona, 37100 Verona, Italy; and
7**Department of Histopathology, Sant’Andrea Hospital, and University of Rome “La Sapienza,” 00185 Rome, Italy

Tóm tắt

Small noncoding microRNAs (miRNAs) can contribute to cancer development and progression and are differentially expressed in normal tissues and cancers. From a large-scale miRnome analysis on 540 samples including lung, breast, stomach, prostate, colon, and pancreatic tumors, we identified a solid cancer miRNA signature composed by a large portion of overexpressed miRNAs. Among these miRNAs are some with well characterized cancer association, such as miR-17-5p , miR-20a , miR-21 , miR-92 , miR-106a , and miR-155 . The predicted targets for the differentially expressed miRNAs are significantly enriched for protein-coding tumor suppressors and oncogenes ( P < 0.0001). A number of the predicted targets, including the tumor suppressors RB1 (Retinoblastoma 1) and TGFBR2 (transforming growth factor, beta receptor II) genes were confirmed experimentally. Our results indicate that miRNAs are extensively involved in cancer pathogenesis of solid tumors and support their function as either dominant or recessive cancer genes.

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Tài liệu tham khảo

V. Ambros Cell 113, 673–676 (2003).

B. R. Cullen Mol. Cell 16, 861–865 (2004).

D. P. Bartel Cell 116, 281–297 (2004).

G. A. Calin, C. D. Dumitru, M. Shimizu, R. Bichi, S. Zupo, E. Noch, H. Aldler, S. Rattan, M. Keating, K. Rai, et al. Proc. Natl. Acad. Sci. USA 99, 15524–15529 (2002).

M. Z. Michael, O. C. SM, N. G. van Holst Pellekaan, G. P. Young, R. J. James Mol. Cancer Res 1, 882–891 (2003).

M. Metzler, M. Wilda, K. Busch, S. Viehmann, A. Borkhardt Genes Chromosomes Cancer 39, 167–169 (2004).

J. Takamizawa, H. Konishi, K. Yanagisawa, S. Tomida, H. Osada, H. Endoh, T. Harano, Y. Yatabe, M. Nagino, Y. Nimura, et al. Cancer Res 64, 3753–3756 (2004).

P. S. Eis, W. Tam, L. Sun, A. Chadburn, Z. Li, M. F. Gomez, E. Lund, J. E. Dahlberg Proc. Natl. Acad. Sci. USA 102, 3627–3632 (2005).

J. A. Chan, A. M. Krichevsky, K. S. Kosik Cancer Res 65, 6029–6033 (2005).

J. Kluiver, S. Poppema, D. de Jong, T. Blokzijl, G. Harms, S. Jacobs, B. J. Kroesen, A. van den Berg J. Pathol 207, 243–249 (2005).

C. M. Croce, G. A. Calin Cell 122, 6–7 (2005).

L. He, J. M. Thomson, M. T. Hemann, E. Hernando-Monge, D. Mu, S. Goodson, S. Powers, C. Cordon-Cardo, S. W. Lowe, G. J. Hannon, S. M. Hammond Nature 435, 828–833 (2005).

K. A. O’Donnell, E. A. Wentzel, K. I. Zeller, C. V. Dang, J. T. Mendell Nature 435, 839–843 (2005).

C.-G. Liu, G. A. Calin, B. Meloon, N. Gamliel, C. Sevignani, M. Ferracin, D. C. Dumitru, M. Shimizu, S. Zupo, M. Dono, et al. Proc. Natl. Acad. Sci. USA 101, 9740–9744 (2004).

J. Lu, G. Getz, E. A. Miska, E. Alvarez-Saavedra, J. Lamb, D. Peck, A. Sweet-Cordero, B. L. Ebert, R. H. Mak, A. A. Ferrando, et al. Nature 435, 834–838 (2005).

G. A. Calin, C. G. Liu, C. Sevignani, M. Ferracin, N. Felli, C. D. Dumitru, M. Shimizu, A. Cimmino, S. Zupo, M. Dono, et al. Proc. Natl. Acad. Sci. USA 101, 11755–11760 (2004).

G. A. Calin, M. Ferracin, A. Cimmino, G. Di Leva, M. Shimizu, S. Wojcik, M. V. Iorio, R. Visone, N. I. Sever, M. Fabbri, et al. N. Engl. J. Med 353, 1793–1801 (2005).

M. V. Iorio, M. Ferracin, C. G. Liu, A. Veronese, R. Spizzo, S. Sabbioni, E. Magri, M. Pedriali, M. Fabbri, M. Campiglio, et al. Cancer Res 65, 7065–7070 (2005).

S. H. Jung, H. Bang, S. Young Biostatistics 6, 157–169 (2005).

B. P. Lewis, C. B. Burge, D. P. Bartel Cell 120, 15–20 (2005).

A. A. Ali, J. N. Marcus, J. P. Harvey, R. Roll, C. P. Hodgson, D. M. Wildrick, A. Chakraborty, B. M. Boman FASEB J 7, 931–937 (1993).

M. B. Buck, P. Fritz, J. Dippon, G. Zugmaier, C. Knabbe Clin. Cancer Res 10, 491–498 (2004).

G. Anumanthan, S. K. Halder, H. Osada, T. Takahashi, P. P. Massion, D. P. Carbone, P. K. Datta Br. J. Cancer 93, 1157–1167 (2005).

N. Yanaihara, N. Caplen, E. Bowman, M. Seike, K. Kumamoto, M. Yi, R. M. Stephens, A. Okamoto, J. Yokota, T. Tanaka, et al. Cancer Cell, in press. (2006).

S. M. Johnson, H. Grosshans, J. Shingara, M. Byrom, R. Jarvis, A. Cheng, E. Labourier, K. L. Reinert, D. Brown, F. J. Slack Cell 120, 635–647 (2005).

A. Cimmino, G. A. Calin, M. Fabbri, M. V. Iorio, M. Ferracin, M. Shimizu, S. E. Wojcik, R. I. Aqeilan, S. Zupo, M. Dono, et al. Proc. Natl. Acad. Sci. USA 102, 13944–13949 (2005).

S. Griffiths-Jones Nucleic Acids Res 32, D109–D111 (2004).

V. G. Tusher, R. Tibshirani, G. Chu Proc. Natl. Acad. Sci. USA 98, 5116–5121 (2001).

R. Tibshirani, T. Hastie, B. Narasimhan, G. Chu Proc. Natl. Acad. Sci. USA 99, 6567–6572 (2002).

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Thông tin xuất bản

Proceedings of the National Academy of Sciences of the United States of America

Tập 103 Số 7

2257-2261

Thông tin tác giả