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PMID: 18362358 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 105 ·No. 13 ·2008-04-01 ·Pages 5166-71

Calin GA, Cimmino A, Fabbri M, Ferracin M, Wojcik SE, Shimizu M, Taccioli C, Zanesi N, Garzon R, Aqeilan RI, Alder H, Volinia S, Rassenti L, Liu X, Liu CG, Kipps TJ, Negrini M, Croce CM

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.

MeSH Terms
Animals Base Sequence Cell Line, Tumor Down-Regulation Female Gene Expression Regulation, Neoplastic/genetics Humans Leukemia/genetics,metabolism,pathology Mice Mice, Nude MicroRNAs/genetics Multigene Family/genetics Proteome/metabolism Proteomics Transcription, Genetic/genetics Xenograft Model Antitumor Assays
Chemicals
MIRN15 microRNA, human MIRN16 microRNA, human MicroRNAs Proteome
Authors & Affiliations
18 authors, click to expand affiliations / ORCID
Calin George A
Human Cancer Genetics Program and Department of Molecular Virology, Immunology, and Medical Genetics, Ohio State University, Columbus, OH 43210, USA. [email protected]
Cimmino Amelia
Fabbri Muller
Ferracin Manuela
Wojcik Sylwia E
Shimizu Masayoshi
Taccioli Cristian
Zanesi Nicola
Garzon Ramiro
Aqeilan Rami I
Alder Hansjuerg
Volinia Stefano
Rassenti Laura
Liu Xiuping
Liu Chang-Gong
Kipps Thomas J
Negrini Massimo
Croce Carlo M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0800121105
Email
[email protected]
Published
2008-04-01
Epub
2008-00-24
Pages
5166-71
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2278188
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0800121105 PMC Full Text View journal details
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