Aberrant expression of miR-9/9* in myeloid progenitors inhibits neutrophil differentiation by post-transcriptional regulation of ERG

Item Type:	Article
Title:	Aberrant expression of miR-9/9* in myeloid progenitors inhibits neutrophil differentiation by post-transcriptional regulation of ERG
Creators Name:	Nowek, K. and Sun, S.M. and Bullinger, L. and Bindels, E.M.J. and Exalto, C. and Dijkstra, M.K. and van Lom, K. and Döhner, H. and Erkeland, S.J. and Löwenberg, B. and Jongen-Lavrencic, M.
Abstract:	Aberrant post-transcriptional regulation by microRNAs (miRNAs) has been shown to be involved in the pathogenesis of acute myeloid leukemia (AML). In a previous study, we performed a large functional screen using a retroviral barcoded miRNA expression library. Here, we report that overexpression of miR-9/9* in myeloid 32D cell line (32D-miR-9/9) had profound impact on granulocyte colony-stimulating factor-induced differentiation. Further in vitro studies showed that enforced expression of miR-9/9 blocked normal neutrophil development in 32D and in primary murine lineage-negative bone marrow cells. We examined the expression of miR-9/9* in a cohort of 647 primary human AMLs. In most cases, miR-9 and miR-9* were significantly upregulated and their expression levels varied according to AML subtype, with the highest expression in MLL-related leukemias harboring 11q23 abnormalities and the lowest expression in AML cases with t(8;21) and biallelic mutations in CEBPA. Gene expression profiling of AMLs with high expression of miR-9/9* and 32D-miR-9/9* identified ETS-related gene (Erg) as the only common potential target. Upregulation of ERG in 32D cells rescued miR-9/9-induced block in neutrophil differentiation. Taken together, this study demonstrates that miR-9/9 are aberrantly expressed in most of AML cases and interfere with normal neutrophil differentiation by downregulation of ERG.
Keywords:	Acute Myeloid Leukemia, Cell Differentiation, Inbred C57BL Mice, Leukemic Gene Expression Regulation, MicroRNAs, Myeloid Progenitor Cells, Neutrophils, Trans-Activators, Transcriptional Regulator ERG, Animals, Mice
Source:	Leukemia
ISSN:	0887-6924
Publisher:	Nature Publishing Group
Volume:	30
Number:	1
Page Range:	229-37
Date:	January 2016
Official Publication:	https://doi.org/10.1038/leu.2015.183
PubMed:	View item in PubMed

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