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MicroRNA-223 is a novel negative regulator of HSP90B1 in CLL

Overview of attention for article published in BMC Cancer, April 2015
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Title
MicroRNA-223 is a novel negative regulator of HSP90B1 in CLL
Published in
BMC Cancer, April 2015
DOI 10.1186/s12885-015-1212-2
Pubmed ID
Authors

Ana E Rodríguez-Vicente, Dalia Quwaider, Rocío Benito, Irena Misiewicz-Krzeminska, María Hernández-Sánchez, Alfonso García de Coca, Rosa Fisac, José-María Alonso, Carolina Zato, Juan Francisco de Paz, Juan Luis García, Ma Eugenia Sarasquete, José Ángel Hernández, Juan M Corchado, Marcos González, Norma C Gutiérrez, Jesús-María Hernández-Rivas

Abstract

MicroRNAs are known to inhibit gene expression by binding to the 3'UTR of the target transcript. Downregulation of miR-223 has been recently reported to have prognostic significance in CLL. However, there is no evidence of the pathogenetic mechanism of this miRNA in CLL patients. By applying next-generation sequencing techniques we have detected a common polymorphism (rs2307842), in 24% of CLL patients, which disrupts the binding site for miR-223 in HSP90B1 3'UTR. We investigated whether miR-223 directly targets HSP90B1 through luciferase assays and ectopic expression of miR-223. Quantitative real-time polymerase chain reaction and western blot were used to determine HSP90B1 expression in CLL patients. The relationship between rs2307842 status, HSP90B1 expression and clinico-biological data were assessed. HSP90B1 is a direct target for miR-223 by interaction with the putative miR-223 binding site. The analysis in paired samples (CD19+ fraction cell and non-CD19+ fraction cell) showed that the presence of rs2307842 and IGHV unmutated genes determined HSP90B1 overexpression in B lymphocytes from CLL patients. These results were confirmed at the protein level by western blot. Of note, HSP90B1 overexpression was independently predictive of shorter time to the first therapy in CLL patients. By contrast, the presence of rs2307842 was not related to the outcome. HSP90B1 is a direct target gene of miR-223. Our results provide a plausible explanation of why CLL patients harboring miR-223 downregulation are associated with a poor outcome, pointing out HSP90B1 as a new pathogenic mechanism in CLL and a promising therapeutic target.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 32 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 32 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 8 25%
Other 6 19%
Student > Ph. D. Student 3 9%
Student > Bachelor 2 6%
Professor 2 6%
Other 5 16%
Unknown 6 19%
Readers by discipline Count As %
Medicine and Dentistry 7 22%
Biochemistry, Genetics and Molecular Biology 6 19%
Agricultural and Biological Sciences 4 13%
Computer Science 2 6%
Chemistry 2 6%
Other 4 13%
Unknown 7 22%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 17 April 2015.
All research outputs
#20,273,512
of 22,805,349 outputs
Outputs from BMC Cancer
#6,491
of 8,297 outputs
Outputs of similar age
#224,074
of 264,900 outputs
Outputs of similar age from BMC Cancer
#219
of 257 outputs
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So far Altmetric has tracked 8,297 research outputs from this source. They receive a mean Attention Score of 4.3. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 257 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.