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Etiology and Pathogenesis
> Tumorigenesis
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Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0510565103.
Published online before print
February 3, 2006. (Laboratory Investigation)
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Abstract |
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A microRNA expression signature of
human solid tumors defines cancer gene targets
Stefano Volinia *+°, George
A. Calin *°, Chang-Gong Liu *, Stefan Ambs §, Amelia
Cimmino *, Fabio Petrocca *, Rosa Visone *, Marilena
Iorio *, Claudia Roldo *, Manuela Ferracin ¶, Robyn
L. Prueitt §, Nozumu Yanaihara §, Giovanni Lanza
¶, Aldo Scarpa ||, Andrea Vecchione **, Massimo
Negrini ¶, Curtis C. Harris §, and Carlo M. Croce
*#
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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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*Department of Molecular
Virology, Immunology, and Medical Genetics and Cancer Comprehensive
Center, Ohio State University, Columbus, OH 43210; §Laboratory
of Human Carcinogenesis, Center for Cancer Research, National Cancer
Institute, National Institutes of Health, Bethesda, MD 20892; +Telethon
Facility-Data Mining for Analysis of DNA Microarrays, Department of
Morphology and Embryology, and ¶Department of Experimental
and Diagnostic Medicine and Interdepartmental Center for Cancer
Research, University of Ferrara, 44100 Ferrara, Italy; ||Department
of Pathology, University of Verona, 37100 Verona, Italy; and **Department
of Histopathology, Sant'Andrea Hospital, and University of Rome
"La Sapienza," 00185 Rome, Italy.
Contributed by Carlo M. Croce, December 9, 2005
Author contributions: S.V., G.A.C., C.-G.L., and C.M.C. designed
research; S.V., G.A.C., C.-G.L., A.C., F.P., R.V., and M.V.I.
performed research; S.V., G.A.C., C.-G.L., S.A., C.R., M.F., R.L.P.,
N.Y., G.L., A.S., A.V., M.N., and C.C.H. contributed new
reagents/analytic tools; S.V. and G.A.C. analyzed data; and S.V.,
G.A.C., and C.M.C. wrote the paper.
Conflict of interest statement: No conflicts declared.
°S.V. and G.A.C. contributed equally to this work.
#To whom correspondence should be addressed. Carlo M. Croce,
E-mail: carlo.croce@osumc.edu
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Copyright © 2006 by the National Academy of
Sciences
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DOI: http://dx.doi.org/10.1073/pnas.0510565103
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Source: http://www.pnas.org/cgi/content/abstract/0510565103v1
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