Authors: Cimmino A; Calin GA; Fabbri M; Iorio MV; Ferracin M; Shimizu M; Wojcik SE; Aqeilan RI; Zupo S; Dono M; Rassenti L; Alder H; Volinia S; Liu CG; Kipps TJ; Negrini M; Croce CM
Abstract: Chronic lymphocytic leukemia (CLL) is the most common human leukemia and is characterized by predominantly nondividing malignant B cells overexpressing the antiapoptotic B cell lymphoma 2 (Bcl2) protein. miR-15a and miR-16-1 are deleted or down-regulated in the majority of CLLs. Here, we demonstrate that miR-15a and miR-16-1 expression is inversely correlated to Bcl2 expression in CLL and that both microRNAs negatively regulate Bcl2 at a posttranscriptional level. BCL2 repression by these microRNAs induces apoptopsis in a leukemic cell line model. Therefore, miR-15 and miR-16 are natural antisense Bcl2 interactors that could be used for therapy of Bcl2-overexpressing tumors.
Keywords: *Apoptosis/genetics; Cell Proliferation; *Gene Expression Regulation, Leukemic; Humans; Leukemia, Lymphocytic, Chronic, B-Cell/*genetics/metabolism; MicroRNAs/genetics/*physiology; Proto-Oncogene Proteins c-bcl-2/*genetics/metabolism; Transcription, Genetic
Journal: Proceedings of the National Academy of Sciences of the United States of America Volume: 102 Issue: 39 Pages: 13944-9 Date: Sept. 17, 2005 PMID: 16166262 |
Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM (2005) miR-15 and miR-16 induce apoptosis by targeting BCL2. Proceedings of the National Academy of Sciences of the United States of America 102: 13944-9.
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