A microRNA expression signature of human solid tumors defines cancer gene targets.
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.
Volinia
Stefano
S
Department of Molecular Virology, Immunology, and Medical Genetics and Cancer Comprehensive Center, Ohio State University, Columbus, OH 43210, USA.
Calin
George A
GA
Liu
Chang-Gong
CG
Ambs
Stefan
S
Cimmino
Amelia
A
Petrocca
Fabio
F
Visone
Rosa
R
Iorio
Marilena
M
Roldo
Claudia
C
Ferracin
Manuela
M
Prueitt
Robyn L
RL
Yanaihara
Nozumu
N
Lanza
Giovanni
G
Scarpa
Aldo
A
Vecchione
Andrea
A
Negrini
Massimo
M
Harris
Curtis C
CC
Croce
Carlo M
CM
D020869:Gene Expression Profiling; D052138:Genes, Neoplasm / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D014407:Tumor Cells, Cultured
D035683:MicroRNAs