MiR-15a and miR-16-1 cluster functions in human leukemia.
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.
Calin
George A
GA
Human Cancer Genetics Program and Department of Molecular Virology, Immunology, and Medical Genetics, Ohio State University, Columbus, OH 43210, USA. gcalin@mdanderson.org
Cimmino
Amelia
A
Fabbri
Muller
M
Ferracin
Manuela
M
Wojcik
Sylwia E
SE
Shimizu
Masayoshi
M
Taccioli
Cristian
C
Zanesi
Nicola
N
Garzon
Ramiro
R
Aqeilan
Rami I
RI
Alder
Hansjuerg
H
Volinia
Stefano
S
Rassenti
Laura
L
Liu
Xiuping
X
Liu
Chang-Gong
CG
Kipps
Thomas J
TJ
Negrini
Massimo
M
Croce
Carlo M
CM
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
C505361:MIRN15 microRNA, human; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D020543:Proteome