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PLoS One. 2012;7(12):e50895. doi: 10.1371/journal.pone.0050895. Epub 2012 Dec 7.

MiR-27a functions as a tumor suppressor in acute leukemia by regulating 14-3-3θ.

Author information

1
Center for Stem Cell Biology and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA. KScheibner@som.umaryland.edu

Abstract

MicroRNAs (miRs) play major roles in normal hematopoietic differentiation and hematopoietic malignancies. In this work, we report that miR-27a, and its coordinately expressed cluster (miR-23a∼miR-27a∼miR-24-2), was down-regulated in acute leukemia cell lines and primary samples compared to hematopoietic stem-progenitor cells (HSPCs). Decreased miR-23a cluster expression in some acute leukemia cell lines was mediated by c-MYC. Replacement of miR-27a in acute leukemia cell lines inhibited cell growth due, at least in part, to increased cellular apoptosis. We identified a member of the anti-apoptotic 14-3-3 family of proteins, which support cell survival by interacting with and negatively regulating pro-apoptotic proteins such as Bax and Bad, as a target of miR-27a. Specifically, miR-27a regulated 14-3-3θ at both the mRNA and protein levels. These data indicate that miR-27a contributes a tumor suppressor-like activity in acute leukemia cells via regulation of apoptosis, and that miR-27a and 14-3-3θ may be potential therapeutic targets.

PMID:
23236401
PMCID:
PMC3517579
DOI:
10.1371/journal.pone.0050895
[Indexed for MEDLINE]
Free PMC Article

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