MicroRNA 29b functions in acute myeloid leukemia.
MicroRNAs (miRNAs) are associated with cytogenetics and molecular subtypes of acute myelogeneous leukemia (AML), but their impact on AML pathogenesis is poorly understood. We have previously shown that miR-29b expression is deregulated in primary AML blasts. In this work, we investigated the functional role of miR-29b in leukemogenesis. Restoration of miR-29b in AML cell lines and primary samples induces apoptosis and dramatically reduces tumorigenicity in a xenograft leukemia model. Transcriptome analysis after ectopic transfection of synthetic miR-29b into leukemia cells indicates that miR-29b target apoptosis, cell cycle, and proliferation pathways. A significant enrichment for apoptosis genes, including MCL-1, was found among the mRNAs inversely correlated with miR-29b expression in 45 primary AML samples. Together, the data support a tumor suppressor role for miR-29 and provide a rationale for the use of synthetic miR-29b oligonucleotides as a novel strategy to improve treatment response in AML.
Garzon
Ramiro
R
Division of Hematology and Oncology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Heaphy
Catherine E A
CE
Havelange
Violaine
V
Fabbri
Muller
M
Volinia
Stefano
S
Tsao
Twee
T
Zanesi
Nicola
N
Kornblau
Steven M
SM
Marcucci
Guido
G
Calin
George A
GA
Andreeff
Michael
M
Croce
Carlo M
CM
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015152:Blotting, Northern; D015153:Blotting, Western; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
C532045:MIRN29a microRNA, human; D035683:MicroRNAs