Dysregulated Expression of the MicroRNA miR-137 and Its Target YBX1 Contribute to the Invasive Characteristics of Malignant Pleural Mesothelioma.

Autor:	Johnson TG; Asbestos Diseases Research Institute, Sydney, Australia., Schelch K; Asbestos Diseases Research Institute, Sydney, Australia., Cheng YY; Asbestos Diseases Research Institute, Sydney, Australia; School of Medicine, University of Sydney, Sydney, Australia., Williams M; Asbestos Diseases Research Institute, Sydney, Australia; School of Medicine, University of Sydney, Sydney, Australia., Sarun KH; Asbestos Diseases Research Institute, Sydney, Australia., Kirschner MB; Division of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland., Kao S; Asbestos Diseases Research Institute, Sydney, Australia; School of Medicine, University of Sydney, Sydney, Australia; Department of Medical Oncology, Chris O'Brien Lifehouse, Sydney, Australia., Linton A; Asbestos Diseases Research Institute, Sydney, Australia; School of Medicine, University of Sydney, Sydney, Australia; Concord Cancer Centre, Concord Repatriation General Hospital, Sydney, Australia., Klebe S; Department of Anatomical Pathology, Flinders University; Department of Anatomical Pathology, SA Pathology at Flinders Medical Centre, Adelaide, Australia., McCaughan BC; Department of Anatomical Pathology, SA Pathology at Flinders Medical Centre, Adelaide, Australia; Sydney Cardiothoracic Surgeons, RPAH Medical Centre, Sydney, Australia., Lin RCY; Asbestos Diseases Research Institute, Sydney, Australia; School of Medical Sciences, University of New South Wales, Sydney, Australia., Pirker C; Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria., Berger W; Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria., Lasham A; Department of Molecular Medicine and Pathology, School of Medical Sciences, University of Auckland, Auckland, New Zealand., van Zandwijk N; Asbestos Diseases Research Institute, Sydney, Australia; School of Medicine, University of Sydney, Sydney, Australia., Reid G; Asbestos Diseases Research Institute, Sydney, Australia; School of Medicine, University of Sydney, Sydney, Australia. Electronic address: glen.reid@sydney.edu.au.
Jazyk:	angličtina
Zdroj:	Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer [J Thorac Oncol] 2018 Feb; Vol. 13 (2), pp. 258-272. Date of Electronic Publication: 2017 Nov 04.
DOI:	10.1016/j.jtho.2017.10.016
Abstrakt:	Introduction: Malignant pleural mesothelioma (MPM) is an aggressive malignancy linked to asbestos exposure. On a genomic level, MPM is characterized by frequent chromosomal deletions of tumor suppressors, including microRNAs. MiR-137 plays a tumor suppressor role in other cancers, so the aim of this study was to characterize it and its target Y-box binding protein 1 (YBX1) in MPM. Methods: Expression, methylation, and copy number status of miR-137 and its host gene MIR137HG were assessed by polymerase chain reaction. Luciferase reporter assays confirmed a direct interaction between miR-137 and Y-box binding protein 1 gene (YBX1). Cells were transfected with a miR-137 inhibitor, miR-137 mimic, and/or YBX1 small interfering RNA, and growth, colony formation, migration and invasion assays were conducted. Results: MiR-137 expression varied among MPM cell lines and tissue specimens, which was associated with copy number variation and promoter hypermethylation. High miR-137 expression was linked to poor patient survival. The miR-137 inhibitor did not affect target levels or growth, but interestingly, it increased miR-137 levels by means of mimic transfection suppressed growth, migration, and invasion, which was linked to direct YBX1 downregulation. YBX1 was overexpressed in MPM cell lines and inversely correlated with miR-137. RNA interference-mediated YBX1 knockdown significantly reduced cell growth, migration, and invasion. Conclusions: MiR-137 can exhibit a tumor-suppressive function in MPM by targeting YBX1. YBX1 knockdown significantly reduces tumor growth, migration, and invasion of MPM cells. Therefore, YBX1 represents a potential target for novel MPM treatment strategies. (Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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