title: MiR-15a and miR-16-1 cluster functions in human leukemia.
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.
authors: Human Cancer Genetics Program and Department of Molecular Virology, Immunology, and Medical Genetics, Ohio State University, Columbus, OH 43210, USA. gcalin@mdanderson.org
authors: George A
authors: GA
authors: Calin
authors: Amelia
authors: A
authors: Cimmino
authors: Muller
authors: M
authors: Fabbri
authors: Manuela
authors: M
authors: Ferracin
authors: Sylwia E
authors: SE
authors: Wojcik
authors: Masayoshi
authors: M
authors: Shimizu
authors: Cristian
authors: C
authors: Taccioli
authors: Nicola
authors: N
authors: Zanesi
authors: Ramiro
authors: R
authors: Garzon
authors: Rami I
authors: RI
authors: Aqeilan
authors: Hansjuerg
authors: H
authors: Alder
authors: Stefano
authors: S
authors: Volinia
authors: Laura
authors: L
authors: Rassenti
authors: Xiuping
authors: X
authors: Liu
authors: Chang-Gong
authors: CG
authors: Liu
authors: Thomas J
authors: TJ
authors: Kipps
authors: Massimo
authors: M
authors: Negrini
authors: Carlo M
authors: CM
authors: Croce
mesh_terms: D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007938:Leukemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D005810:Multigene Family / Q000235:genetics*; D020543:Proteome / Q000378:metabolism; D040901:Proteomics; D014158:Transcription, Genetic / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: C505361:MIRN15 microRNA, human; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D020543:Proteome