4.1 Article

Imbalanced expression of polycistronic miRNA in acute myeloid leukemia

Journal

INTERNATIONAL JOURNAL OF HEMATOLOGY
Volume 106, Issue 6, Pages 811-819

Publisher

SPRINGER JAPAN KK
DOI: 10.1007/s12185-017-2314-1

Keywords

miR-1; miR-133; EVI1; AML

Categories

Funding

  1. Japan Society for the Promotion of Science
  2. Japan Leukemia Research Fund
  3. Research Program on Hepatitis from Japan Agency for Medical Research and Development, AMED
  4. Grants-in-Aid for Scientific Research [15K06838, 17H04212] Funding Source: KAKEN

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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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