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Increased Expression of miR-23a Mediates a Loss of Expression in the RAF Kinase Inhibitor Protein RKIP

Overview of attention for article published in Cancer Research, June 2016
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (85th percentile)
  • High Attention Score compared to outputs of the same age and source (88th percentile)

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1 news outlet
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3 X users

Citations

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46 Dimensions

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31 Mendeley
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Title
Increased Expression of miR-23a Mediates a Loss of Expression in the RAF Kinase Inhibitor Protein RKIP
Published in
Cancer Research, June 2016
DOI 10.1158/0008-5472.can-15-3049
Pubmed ID
Authors

Stefan Hatzl, Olivia Geiger, Maja Kim Kuepper, Veronica Caraffini, Till Seime, Tobias Furlan, Erika Nussbaumer, Rotraud Wieser, Martin Pichler, Marcel Scheideler, Katarzyna Nowek, Mojca Jongen-Lavrencic, Franz Quehenberger, Albert Wölfler, Jakob Troppmair, Heinz Sill, Armin Zebisch

Abstract

RAF kinase inhibitor protein (RKIP) is a seminal regulator of intracellular signaling and exhibits both anti-metastatic and anti-tumorigenic properties. Decreased expression of RKIP has been described in several human malignancies, including acute myeloid leukemia (AML). As the mechanisms leading to RKIP loss in AML are still unclear, we aimed to analyze the potential involvement of micro-RNAs (miRNAs) within this study. miRNA microarray and qPCR data of more than 400 AML patient specimens revealed correlation between decreased expression of RKIP and increased expression of miR-23a, a member of the miR-23a/27a/24-2 cluster. In functional experiments, overexpression of miR-23a decreased RKIP mRNA and protein expression, whereas miR-23a inhibition caused the opposite effect. By employing an RKIP 3'UTR luciferase reporter construct with and without mutation or deletion of the putative miR-23a binding site, we could show that RKIP modulation by miR-23a is mediated via direct binding to this region. Importantly, miR-23a overexpression induced a significant increase of proliferation in hematopoietic cells. Simultaneous transfection of an RKIP expression construct lacking the miR-23a binding sites reversed this phenotype, indicating that this effect is truly mediated via downregulation of RKIP. Finally, by analyzing more than 4300 primary patient specimens via database retrieval from The Cancer Genome Atlas (TCGA), we could highlight the importance of the miR-23a/RKIP axis in a broad range of human cancer entities. In conclusion, we have identified miR-23a as a negative regulator of RKIP expression in AML and have provided data that suggest the importance of our observation beyond this tumor entity.

X Demographics

X Demographics

The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 31 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 31 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 23%
Student > Master 5 16%
Student > Bachelor 4 13%
Researcher 3 10%
Professor 2 6%
Other 5 16%
Unknown 5 16%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 10 32%
Medicine and Dentistry 5 16%
Agricultural and Biological Sciences 4 13%
Immunology and Microbiology 1 3%
Unspecified 1 3%
Other 2 6%
Unknown 8 26%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 11. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 August 2016.
All research outputs
#2,710,865
of 22,862,742 outputs
Outputs from Cancer Research
#2,261
of 17,879 outputs
Outputs of similar age
#50,737
of 352,659 outputs
Outputs of similar age from Cancer Research
#56
of 516 outputs
Altmetric has tracked 22,862,742 research outputs across all sources so far. Compared to these this one has done well and is in the 87th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 17,879 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.8. This one has done well, scoring higher than 87% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 352,659 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 85% of its contemporaries.
We're also able to compare this research output to 516 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 88% of its contemporaries.