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In-depth characterization of the microRNA transcriptome in a leukemia progression model

Overview of attention for article published in Genome Research, November 2008
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Title
In-depth characterization of the microRNA transcriptome in a leukemia progression model
Published in
Genome Research, November 2008
DOI 10.1101/gr.077578.108
Pubmed ID
Authors

Florian Kuchenbauer, Ryan D. Morin, Bob Argiropoulos, Oleh I. Petriv, Malachi Griffith, Michael Heuser, Eric Yung, Jessica Piper, Allen Delaney, Anna-Liisa Prabhu, Yongjun Zhao, Helen McDonald, Thomas Zeng, Martin Hirst, Carl L. Hansen, Marco A. Marra, R. Keith Humphries

Abstract

MicroRNAs (miRNAs) have been shown to play important roles in physiological as well as multiple malignant processes, including acute myeloid leukemia (AML). In an effort to gain further insight into the role of miRNAs in AML, we have applied the Illumina massively parallel sequencing platform to carry out an in-depth analysis of the miRNA transcriptome in a murine leukemia progression model. This model simulates the stepwise conversion of a myeloid progenitor cell by an engineered overexpression of the nucleoporin 98 (NUP98)-homeobox HOXD13 fusion gene (ND13), to aggressive AML inducing cells upon transduction with the oncogenic collaborator Meis1. From this data set, we identified 307 miRNA/miRNA species in the ND13 cells and 306 miRNA/miRNA species in ND13+Meis1 cells, corresponding to 223 and 219 miRNA genes. Sequence counts varied between two and 136,558, indicating a remarkable expression range between the detected miRNA species. The large number of miRNAs expressed and the nature of differential expression suggest that leukemic progression as modeled here is dictated by the repertoire of shared, but differentially expressed miRNAs. Our finding of extensive sequence variations (isomiRs) for almost all miRNA and miRNA species adds additional complexity to the miRNA transcriptome. A stringent target prediction analysis coupled with in vitro target validation revealed the potential for miRNA-mediated release of oncogenes that facilitates leukemic progression from the preleukemic to leukemia inducing state. Finally, 55 novel miRNAs species were identified in our data set, adding further complexity to the emerging world of small RNAs.

Mendeley readers

The data shown below were compiled from readership statistics for 146 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 9 6%
United Kingdom 4 3%
Canada 2 1%
Russian Federation 1 <1%
Spain 1 <1%
Japan 1 <1%
Czech Republic 1 <1%
Unknown 127 87%

Demographic breakdown

Readers by professional status Count As %
Researcher 50 34%
Student > Ph. D. Student 48 33%
Student > Master 12 8%
Professor > Associate Professor 10 7%
Student > Bachelor 7 5%
Other 19 13%
Readers by discipline Count As %
Agricultural and Biological Sciences 102 70%
Biochemistry, Genetics and Molecular Biology 21 14%
Medicine and Dentistry 10 7%
Unspecified 3 2%
Computer Science 3 2%
Other 7 5%