title: A microRNA expression signature of human solid tumors defines cancer gene targets.
abstract: 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.
authors.affiliation: Department of Molecular Virology, Immunology, and Medical Genetics and Cancer Comprehensive Center, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Stefano
authors.initials: S
authors.lastname: Volinia
authors.forename: George A
authors.initials: GA
authors.lastname: Calin
authors.forename: Chang-Gong
authors.initials: CG
authors.lastname: Liu
authors.forename: Stefan
authors.initials: S
authors.lastname: Ambs
authors.forename: Amelia
authors.initials: A
authors.lastname: Cimmino
authors.forename: Fabio
authors.initials: F
authors.lastname: Petrocca
authors.forename: Rosa
authors.initials: R
authors.lastname: Visone
authors.forename: Marilena
authors.initials: M
authors.lastname: Iorio
authors.forename: Claudia
authors.initials: C
authors.lastname: Roldo
authors.forename: Manuela
authors.initials: M
authors.lastname: Ferracin
authors.forename: Robyn L
authors.initials: RL
authors.lastname: Prueitt
authors.forename: Nozumu
authors.initials: N
authors.lastname: Yanaihara
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lanza
authors.forename: Aldo
authors.initials: A
authors.lastname: Scarpa
authors.forename: Andrea
authors.initials: A
authors.lastname: Vecchione
authors.forename: Massimo
authors.initials: M
authors.lastname: Negrini
authors.forename: Curtis C
authors.initials: CC
authors.lastname: Harris
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
mesh_terms: 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
chemical_list: D035683:MicroRNAs