International Journal of Hematology

DOI: 10.1007/s12185-017-2314-1 Pages: 811-819

Imbalanced expression of polycistronic miRNA in acute myeloid leukemia

1. Tokai University, Division of Hematological Malignancy, Institute of Medical Sciences

2. Tokai University School of Medicine, Department of Hematology and Oncology

3. University of Technology Malaysia, Department of Electronic Systems Engineering, Malaysia-Japan International Institute of Technology

4. International Islamic University Malaysia, Department of Biotechnology, Kulliyyah of Science

5. Tokai University School of Medicine, Department of Emergency and Critical Care Medicine

6. University of Miyazaki, Department of Medical Sciences, Faculty of Medicine

7. Kyoto University, Department of Cardiovascular Medicine, Graduate School of Medicine

Correspondence to:
Ai Kotani
Tel: +81-463-93-1121
Email: aikotani@k-lab.jp

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Abstract

miR-1 and miR-133 are clustered on the same chromosomal loci and are transcribed together as a single transcript that is positively regulated by ecotropic virus integration site-1 (EVI1). Previously, we described how miR-133 has anti-tumorigenic potential through repression of EVI1 expression. It has also been reported that miR-1 is oncogenic in the case of acute myeloid leukemia (AML). Here, we show that expression of miR-1 and miR-133, which have distinct functions, is differentially regulated between AML cell lines. Interestingly, the expression of miR-1 and EVI1, which binds to the promoter of the miR-1/miR-133 cluster, is correlative. The expression levels of TDP-43, an RNA-binding protein that has been reported to increase the expression, but inhibits the activity, of miR-1, were not correlated with expression levels of miR-1 in AML cells. Taken together, our observations raise the possibility that the balance of polycistronic miRNAs is regulated post-transcriptionally in a hierarchical manner possibly involving EVI1, suggesting that the deregulation of this balance may play some role in AML cells with high EVI1 expression.

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