Journal article
Loss of miR-223 and JNK signaling contribute to elevated stathmin in malignant pleural mesothelioma
Molecular Cancer Research, Vol.13(7), pp.1106-1118
2015
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.
Implications: miR-223 regulates STMN1 in MPM, and both are in turn regulated by the JNK signaling pathway. As such, miR-223 and STMN1 play an important role in regulating MPM cell motility and may be therapeutic targets.
Details
- Title
- Loss of miR-223 and JNK signaling contribute to elevated stathmin in malignant pleural mesothelioma
- Authors/Creators
- K.A. Birnie (Author/Creator) - Harry Perkins Institute of Medical ResearchY.Y. Yip (Author/Creator) - The University of MelbourneD.C.H. Ng (Author/Creator) - The University of MelbourneM.B. Kirschner (Author/Creator) - Asbestos Diseases Research InstituteG. Reid (Author/Creator) - Asbestos Diseases Research InstituteC.M. Prêle (Author/Creator) - Harry Perkins Institute of Medical ResearchA.W. Musk (Author/Creator) - The University of Western AustraliaY.C.G. Lee (Author/Creator) - Harry Perkins Institute of Medical ResearchP.J. Thompson (Author/Creator) - Harry Perkins Institute of Medical ResearchS.E. Mutsaers (Author/Creator) - Harry Perkins Institute of Medical ResearchB. Badrian (Author/Creator) - Harry Perkins Institute of Medical Research
- Publication Details
- Molecular Cancer Research, Vol.13(7), pp.1106-1118
- Publisher
- American Association for Cancer Research
- Identifiers
- 991005544479407891
- Copyright
- © 2015 by the American Association for Cancer Research.
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites
Metrics
41 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.196 Micro & Long Noncoding RNA
- 1.196.68 MicroRNA in Cancer
- Web Of Science research areas
- Cell Biology
- Oncology
- ESI research areas
- Molecular Biology & Genetics