miR-15 and miR-16 induce apoptosis by targeting BCL2.
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.
Cimmino
Amelia
A
Department of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus OH 43210, USA.
Calin
George Adrian
GA
Fabbri
Muller
M
Iorio
Marilena V
MV
Ferracin
Manuela
M
Shimizu
Masayoshi
M
Wojcik
Sylwia E
SE
Aqeilan
Rami I
RI
Zupo
Simona
S
Dono
Mariella
M
Rassenti
Laura
L
Alder
Hansjuerg
H
Volinia
Stefano
S
Liu
Chang-Gong
CG
Kipps
Thomas J
TJ
Negrini
Massimo
M
Croce
Carlo M
CM
D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
C505361:MIRN15 microRNA, human; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2