Complexity of miR-223 regulation by CEBPA in human AML

Leuk Res. 2010 May;34(5):672-6. doi: 10.1016/j.leukres.2009.11.019. Epub 2009 Dec 16.

Abstract

microRNA-223 (miR-223) can trigger normal granulopoiesis. miR-223 expression is regulated by two distinct CEBPA (CCAAT/enhancer binding protein-alpha) sites. Here, we report that miR-223 is largely suppressed in cells from acute myeloid leukemia (AML) patients. By sequencing, we found that miR-223 suppression in AML is not caused by DNA sequence alterations, nor is it mediated by promoter hypermethylation. The analysis of the individual contribution of both CEBPA sites to miR-223 regulation identified the site upstream of the miR-223 primary transcript as the predominant regulatory element. Our results suggest that miR-223 suppression in AML is caused by impaired miR-223 upstream factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Blotting, Western
  • CCAAT-Enhancer-Binding Proteins / genetics*
  • Electrophoretic Mobility Shift Assay
  • Gene Expression
  • Gene Expression Regulation, Leukemic / genetics*
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • MicroRNAs / genetics*
  • Molecular Sequence Data
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • CCAAT-Enhancer-Binding Proteins
  • CEBPA protein, human
  • MIRN223 microRNA, human
  • MicroRNAs