Loss of miR-223 and JNK signaling contribute to elevated Stathmin in malignant pleural mesothelioma

Birnie, Kimberly A., Yip, Yan Y., Ng, Dominic C. H., Kirschner, Michaela B., Reid, Glen, Prele, Cecilia M., Musk, Arthur W. (Bill), Lee, Y. C. Gary, Thompson, Philip J., Mutsaers, Steven E. and Badrian, Bahareh (2015) Loss of miR-223 and JNK signaling contribute to elevated Stathmin in malignant pleural mesothelioma. Molecular Cancer Research, 13 7: 1106-1118. doi:10.1158/1541-7786.MCR-14-0442


Author Birnie, Kimberly A.
Yip, Yan Y.
Ng, Dominic C. H.
Kirschner, Michaela B.
Reid, Glen
Prele, Cecilia M.
Musk, Arthur W. (Bill)
Lee, Y. C. Gary
Thompson, Philip J.
Mutsaers, Steven E.
Badrian, Bahareh
Title Loss of miR-223 and JNK signaling contribute to elevated Stathmin in malignant pleural mesothelioma
Journal name Molecular Cancer Research   Check publisher's open access policy
ISSN 1541-7786
1557-3125
Publication date 2015-07-01
Sub-type Article (original research)
DOI 10.1158/1541-7786.MCR-14-0442
Open Access Status Not Open Access
Volume 13
Issue 7
Start page 1106
End page 1118
Total pages 13
Place of publication Philadelphia, PA, United States
Publisher American Association for Cancer Research
Language eng
Abstract Malignant pleural mesothelioma (MPM) is often fatal, and studies have revealed that aberrant 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) signaling, but whether this occurs in MPM and whether miR-223 plays a role are 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 with 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 while STMN1 was reduced following the re-expression of the JNK isoforms in JNK-null murine embryonic fibroblasts, and STMN1 was reduced in MPM cell lines following the activation of JNK signaling.
Keyword Down regulation
Hepatocellular carcinoma
Cell proliferation
Cancer
Microrna-223
Expression
Pathogenesis
Genes
Progression
Biomarker
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Biomedical Sciences Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 13 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 17 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 23 Aug 2015, 11:31:24 EST by System User on behalf of Scholarly Communication and Digitisation Service