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

2008; National Academy of Sciences; Volume: 105; Issue: 13 Linguagem: Inglês

10.1073/pnas.0800121105

1091-6490

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

Circular RNAs in diseases

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.