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Loss of miR-223 and JNK Signaling Contribute to Elevated Stathmin in Malignant Pleural Mesothelioma

Overview of attention for article published in Molecular Cancer Research, July 2015
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Title
Loss of miR-223 and JNK Signaling Contribute to Elevated Stathmin in Malignant Pleural Mesothelioma
Published in
Molecular Cancer Research, July 2015
DOI 10.1158/1541-7786.mcr-14-0442
Pubmed ID
Authors

Kimberly A. Birnie, Yan Y. Yip, Dominic C.H. Ng, Michaela B. Kirschner, Glen Reid, Cecilia M. Prêle, Arthur W. (Bill) Musk, Y.C. Gary Lee, Philip J. Thompson, Steven E. Mutsaers, Bahareh Badrian

Abstract

Malignant pleural mesothelioma (MPM) is often fatal and studies have revealed that aberrant microRNAs (miRNAs) contribute to MPM development and aggressiveness. Here a screen of miRNAs identified reduced levels of miR-223 in MPM patient specimens. Interestingly, miR-223 targets Stathmin (STMN1), a microtubule regulator that has been associated with MPM. However, whether miR-223 regulates STMN1 in MPM and the functions of miR-223 and STMN1 in this disease are yet to be determined. STMN1 is also regulated by c-Jun N-terminal kinase (JNK) signalling but whether this occurs in MPM and whether miR-223 plays a role is unknown. The relationship between STMN1, miR-223 and JNK was assessed using MPM cell lines, cells from pleural effusions and MPM tissue. Evidence indicates that miR-223 is decreased in all MPM tissue compared to normal/healthy tissue. Conversely, STMN1 expression was higher in MPM cell lines when compared with primary mesothelial cell controls. Following overexpression of miR-223 in MPM cell lines, STMN1 levels were reduced, cell motility was inhibited and tubulin acetylation induced. Knockdown of STMN1 using siRNAs, led to inhibition of MPM cell proliferation and motility. Finally, miR-223 levels increased whilst STMN1 was reduced following the re-expression of the JNK isoforms in JNK-null murine embryonic fibroblasts (MEFs) and STMN1 was reduced in MPM cell lines following the activation of JNK signalling. miR-223 regulates STMN1 in MPM and both are in turn regulated by the JNK signalling pathway. As such, miR-223 and STMN1 play an important role in regulating MPM cell motility and may be therapeutic targets.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 26 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 4%
Kazakhstan 1 4%
Australia 1 4%
Unknown 23 88%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 19%
Researcher 4 15%
Professor > Associate Professor 4 15%
Student > Bachelor 2 8%
Student > Postgraduate 2 8%
Other 3 12%
Unknown 6 23%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 35%
Agricultural and Biological Sciences 4 15%
Medicine and Dentistry 3 12%
Immunology and Microbiology 2 8%
Nursing and Health Professions 1 4%
Other 0 0%
Unknown 7 27%
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 31 March 2016.
All research outputs
#20,267,098
of 22,797,621 outputs
Outputs from Molecular Cancer Research
#1,712
of 1,882 outputs
Outputs of similar age
#219,332
of 262,578 outputs
Outputs of similar age from Molecular Cancer Research
#25
of 26 outputs
Altmetric has tracked 22,797,621 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,882 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.1. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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 262,578 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 26 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.