Статья

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

Stefano Volinia*Department of Molecular Virology, Immunology, and Medical Genetics and Cancer Comprehensive Center, Ohio State University, Columbus, OH 43210;George A. Calin*Department of Molecular Virology, Immunology, and Medical Genetics and Cancer Comprehensive Center, Ohio State University, Columbus, OH 43210;Chang‐Gong Liu*Department of Molecular Virology, Immunology, and Medical Genetics and Cancer Comprehensive Center, Ohio State University, Columbus, OH 43210;Stefan AmbsLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;Amelia Cimmino*Department of Molecular Virology, Immunology, and Medical Genetics and Cancer Comprehensive Center, Ohio State University, Columbus, OH 43210;Fabio Petrocca*Department of Molecular Virology, Immunology, and Medical Genetics and Cancer Comprehensive Center, Ohio State University, Columbus, OH 43210;Rosa Visone*Department of Molecular Virology, Immunology, and Medical Genetics and Cancer Comprehensive Center, Ohio State University, Columbus, OH 43210;Marilena V. Iorio*Department of Molecular Virology, Immunology, and Medical Genetics and Cancer Comprehensive Center, Ohio State University, Columbus, OH 43210;Claudia Roldo*Department of Molecular Virology, Immunology, and Medical Genetics and Cancer Comprehensive Center, Ohio State University, Columbus, OH 43210;Manuela FerracinDepartment of Experimental and Diagnostic Medicine and Interdepartmental Center for Cancer Research, University of Ferrara, 44100 Ferrara, Italy;Robyn L. PrueittLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;Nozumu YanaiharaLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;Giovanni LanzaDepartment of Experimental and Diagnostic Medicine and Interdepartmental Center for Cancer Research, University of Ferrara, 44100 Ferrara, Italy;Aldo ScarpaDepartment of Pathology, University of Verona, 37100 Verona, Italy; andAndrea VecchioneMassimo NegriniDepartment of Experimental and Diagnostic Medicine and Interdepartmental Center for Cancer Research, University of Ferrara, 44100 Ferrara, Italy;Curtis C. HarrisCenter for Cancer ResearchCarlo M. Croce*Department of Molecular Virology, Immunology, and Medical Genetics and Cancer Comprehensive Center, Ohio State University, Columbus, OH 43210;

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ABI

Аннотация

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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Идентификаторы

DOI: 10.1073/pnas.0510565103

Цитирования и источники

Цитирований: 4Использованных источников: 0

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