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

被引：2783
作者：
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 [1 ]
机构：
[1] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA
[2] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA
[3] Univ Ferrara, Interdept Ctr Canc Res, Dept Expt & Diagnost Med, I-44100 Ferrara, Italy
[4] Inst Nazl Ric Canc, I-16123 Genoa, Italy
[5] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2005年 / 102卷 / 39期
关键词：
microRNAs; translation; leukemia;
D O I：
10.1073/pnas.0506654102
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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-15w and miR-16 are natural antisense Bcl2 interactors that could be used for therapy of Bcl2-overexpressing tumors.
引用
收藏
页码：13944 / 13949
页数：6
相关论文
共 31 条
[1]   PREFERENTIAL LINKAGE OF BCL-2 TO IMMUNOGLOBULIN LIGHT CHAIN GENE IN CHRONIC LYMPHOCYTIC-LEUKEMIA [J].
ADACHI, M ;
TEFFERI, A ;
GREIPP, PR ;
KIPPS, TJ ;
TSUJIMOTO, Y .
JOURNAL OF EXPERIMENTAL MEDICINE, 1990, 171 (02) :559-564
[2]  
Ausubel FA, 1995, CURRENT PROTOCOLS MO
[3]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[4]   Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia [J].
Calin, GA ;
Dumitru, CD ;
Shimizu, M ;
Bichi, R ;
Zupo, S ;
Noch, E ;
Aldler, H ;
Rattan, S ;
Keating, M ;
Rai, K ;
Rassenti, L ;
Kipps, T ;
Negrini, M ;
Bullrich, F ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (24) :15524-15529
[5]   Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers [J].
Calin, GA ;
Sevignani, C ;
Dan Dumitru, C ;
Hyslop, T ;
Noch, E ;
Yendamuri, S ;
Shimizu, M ;
Rattan, S ;
Bullrich, F ;
Negrini, M ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (09) :2999-3004
[6]   MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias [J].
Calin, GA ;
Liu, CG ;
Sevignani, C ;
Ferracin, M ;
Felli, N ;
Dumitru, CD ;
Shimizu, M ;
Cimmino, A ;
Zupo, S ;
Dono, M ;
Dell'Aquila, ML ;
Alder, H ;
Rassenti, L ;
Kipps, TJ ;
Bullrich, F ;
Negrini, M ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (32) :11755-11760
[7]  
CALIN GA, 2005, IN PRESS N ENGL J ME
[8]   Mechanisms of disease: Chronic lymphocytic leukemia [J].
Chiorazzi, N ;
Rai, KR ;
Ferrarini, M .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 352 (08) :804-815
[9]   The Bcl-2 family: roles in cell survival and oncogenesis [J].
Cory, S ;
Huang, DCS ;
Adams, JM .
ONCOGENE, 2003, 22 (53) :8590-8607
[10]   The BCL2 family: Regulators of the cellular life-or-death switch [J].
Cory, S ;
Adams, JM .
NATURE REVIEWS CANCER, 2002, 2 (09) :647-656
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