Authors: Scheibner KA; Teaboldt B; Hauer MC; Chen X; Cherukuri S; Guo Y; Kelley SM; Liu Z; Baer MR; Heimfeld S; Civin CI
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 approximately miR-27a approximately 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 14-3-3theta 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 14-3-3theta may be potential therapeutic targets.
Keywords: 14-3-3 Proteins/*genetics/metabolism; Apoptosis/genetics; Apoptosis Regulatory Proteins/genetics/metabolism; Cell Line, Tumor; Down-Regulation; Gene Expression Regulation, Neoplastic; Humans; Leukemia/*genetics/metabolism; MicroRNAs/*genetics/metabolism; Tumor Suppressor Proteins/*genetics/metabolism|
Journal: PloS one Volume: 7 Issue: 12 Pages: e50895 Date: Dec. 14, 2012 PMID: 23236401 |
Scheibner KA, Teaboldt B, Hauer MC, Chen X, Cherukuri S, Guo Y, Kelley SM, Liu Z, Baer MR, Heimfeld S, Civin CI (2012) MiR-27a functions as a tumor suppressor in acute leukemia by regulating 14-3-3θ. PloS one 7: e50895.
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