1. Ultraconserved Regions Encoding ncRNAs Are Altered in Human Leukemias and Carcinomas
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Muller Fabbri, Manuela Ferracin, Chang Gong Liu, Laura Z. Rassenti, Giovanni Lanza, Flavia Pichiorri, Hansjuerg Alder, Simona Zupo, Xiuping Liu, Riccardo Spizzo, Amelia Cimmino, Massimo Negrini, Stefano Volinia, Thomas J. Kipps, Eun Joo Lee, Vlad Herlea, Esmerina Tili, Thomas D. Schmittgen, Carlo M. Croce, George A. Calin, Terry Hyslop, Cristian Taccioli, Masayoshi Shimizu, Sylwia E. Wojcik, Simona Rossi, Cinzia Sevignani, Laura Gramantieri, CALIN G., A, LIU C., G, Ferracin, Manuela, Hyslop, T, Spizzo, R, Sevignani, C, Fabbri, M, Cimmino, A, LEE E., J, WOJCIK S., E, Shimizu, M, Tili, E, Rossi, S, Taccioli, C, Pichiorri, F, Liu, X, Zupo, S, Herlea, V, Gramantieri, L, Lanza, G, Alder, H, Rassenti, L, Volinia, S, SCHMITTGEN T., D, KIPPS T., J, Negrini, M., and Croce, C. M.
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EXPRESSION ,Cancer Research ,RNA, Untranslated ,Molecular Sequence Data ,CELLCYCLE ,Biology ,medicine.disease_cause ,HUMAN CANCERS ,microRNA ,medicine ,HUMAN GENOME ,Cluster Analysis ,Humans ,Gene ,SIGNATURES ,Conserved Sequence ,Genetics ,Regulation of gene expression ,Leukemia ,IDENTIFICATION ,Base Sequence ,CHRONIC LYMPHOCYTIC-LEUKEMIA ,Sequence Analysis, RNA ,Gene Expression Profiling ,Chromosomal fragile site ,Carcinoma ,Oncogenes ,Cell Biology ,HUMAN MICRORNA GENES ,NONCODING SEQUENCES ,Non-coding RNA ,Gene Expression Regulation, Neoplastic ,Gene expression profiling ,MicroRNAs ,Oncology ,B-CELL LYMPHOMAS ,RNA ,Human genome ,Carcinogenesis - Abstract
SummaryNoncoding RNA (ncRNA) transcripts are thought to be involved in human tumorigenesis. We report that a large fraction of genomic ultraconserved regions (UCRs) encode a particular set of ncRNAs whose expression is altered in human cancers. Genome-wide profiling revealed that UCRs have distinct signatures in human leukemias and carcinomas. UCRs are frequently located at fragile sites and genomic regions involved in cancers. We identified certain UCRs whose expression may be regulated by microRNAs abnormally expressed in human chronic lymphocytic leukemia, and we proved that the inhibition of an overexpressed UCR induces apoptosis in colon cancer cells. Our findings argue that ncRNAs and interaction between noncoding genes are involved in tumorigenesis to a greater extent than previously thought.
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