MiR-15a and miR-16-1 cluster functions in human leukemia

George A. Calin, Amelia Cimmino, Muller Fabbri, Manuela Ferracin, Sylwia E. Wojcik, Masayoshi Shimizu, Cristian Taccioli, Nicola Zanesi, Ramiro Garzon, Rami I. Aqeilan, Hansjuerg Alder, Stefano Volinia, Laura Rassenti, Xiuping Liu, Chang Gong Liu, Thomas J. Kipps, Massimo Negrini, Carlo M. Croce

Research output: Contribution to journalArticlepeer-review

675 Scopus citations

Abstract

MicroRNAs (miRNAs) are short noncoding RNAs regulating gene expression that play roles in human diseases, including cancer. Each miRNA is predicted to regulate hundreds of transcripts, but only few have experimental validation. In chronic lymphocytic leukemia (CLL), the most common adult human leukemia, miR-15a and miR-16-1 are lost or down-regulated in the majority of cases. After our previous work indicating a tumor suppressor function of miR-15a/16-1 by targeting the BCL2 oncogene, here, we produced a high-throughput profiling of genes modulated by miR-15a/16-1 in a leukemic cell line model (MEG-01) and in primary CLL samples. By combining experimental and bioinformatics data, we identified a miR-15a/16-1-gene signature in leukemic cells. Among the components of the miR-15a/16-1 signature, we observed a statistically significant enrichment in AU-rich elements (AREs). By examining the Gene Ontology (GO) database, a significant enrichment in cancer genes (such as MCL1, BCL2, ETS1, or JUN) that directly or indirectly affect apoptosis and cell cycle was found.

Original languageAmerican English
Pages (from-to)5166-5171
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number13
DOIs
StatePublished - 1 Apr 2008
Externally publishedYes

Keywords

  • Cancer
  • MicroRNA
  • Targets

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