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PMID: 16166262 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

miR-15 and miR-16 induce apoptosis by targeting BCL2.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 102 ·No. 39 ·2005-09-27 ·Pages 13944-9

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.

MeSH Terms
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
Chemicals
MIRN15 microRNA, human MIRN16 microRNA, human MicroRNAs Proto-Oncogene Proteins c-bcl-2
Authors & Affiliations
17 authors, click to expand affiliations / ORCID
Cimmino Amelia
Department of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus OH 43210, USA.
Calin George Adrian
Fabbri Muller
Iorio Marilena V
Ferracin Manuela
Shimizu Masayoshi
Wojcik Sylwia E
Aqeilan Rami I
Zupo Simona
Dono Mariella
Rassenti Laura
Alder Hansjuerg
Volinia Stefano
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
0027-8424
DOI
10.1073/pnas.0506654102
Published
2005-09-27
Epub
2005-00-15
Pages
13944-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1236577
Subset
IM
Grants
NCI NIH HHS · P30CA56036 · United States
NCI NIH HHS · P01CA76259 · United States
NCI NIH HHS · P01 CA081534 · United States
NCI NIH HHS · P01 CA076259 · United States
NCI NIH HHS · P01CA81534 · United States
NCI NIH HHS · P30 CA056036 · United States
Corrections
ErratumIn
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External Links
PubMed source DOI: 10.1073/pnas.0506654102 PMC Full Text View journal details
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