Title
Altered Runx1 subnuclear targeting enhances myeloid cell proliferation and blocks differentiation by activating a miR-24/MKP-7/MAPK network
UMMS Affiliation
Department of Cell Biology
Publication Date
2009-10-15
Document Type
Article
Subjects
Cell Proliferation; Cell Differentiation; Leukemia, Myeloid, Acute; Core Binding Factor Alpha 2 Subunit; Humans; MicroRNAs; Transcription Factors; Mitogen-Activated Protein Kinase Phosphatases
Disciplines
Cell Biology
Abstract
Disruption of Runx1/AML1 subnuclear localization, either by a single amino acid substitution or by a chromosomal translocation [e.g., t(8;21)], is linked to the etiology of acute myeloid leukemia (AML). Here, we show that this defect induces a select set of micro-RNAs (miR) in myeloid progenitor cells and AML patients with t(8;21). Both Runx1 and the t(8;21)-encoded AML1-ETO occupy the miR-24-23-27 locus and reciprocally control miR-24 transcription. miR-24 directly downregulates mitogen-activated protein kinase (MAPK) phosphatase-7 and enhances phosphorylation of both c-jun-NH(2)-kinase and p38 kinases. Expression of miR-24 stimulates myeloid cell growth, renders proliferation independent of interleukin-3, and blocks granulocytic differentiation. Thus, compromised Runx1 function induces a miR-dependent mechanism that, through MAPK signaling, enhances myeloid proliferation but blocks differentiation--key steps that contribute to leukemia.
DOI of Published Version
10.1158/0008-5472.CAN-09-1567
Source
Cancer Res. 2009 Nov 1;69(21):8249-55. Epub 2009 Oct 13. Link to article on publisher's site
Journal/Book/Conference Title
Cancer research
Related Resources
PubMed ID
19826043
Repository Citation
Zaidi SK, Dowdy CR, Van Wijnen AJ, Lian JB, Raza A, Stein JL, Croce CM, Stein GS. (2009). Altered Runx1 subnuclear targeting enhances myeloid cell proliferation and blocks differentiation by activating a miR-24/MKP-7/MAPK network. Cell and Developmental Biology Publications. https://doi.org/10.1158/0008-5472.CAN-09-1567. Retrieved from https://escholarship.umassmed.edu/cellbiology_pp/87