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

Thomas Johnson, Karin Schelch, Yuen Yee Cheng, Marissa Williams, Kadir Sarun, Michaela Kirschner, Steven Kao, Anthony Linton, Sonja Klebe, Brian McCaughan, Ruby Lin, Christine Pirker, Walter Berger, Annette Lasham, Nico van Zandwijk, Glen Reid

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)258-272
Number of pages15
JournalJournal of Thoracic Oncology
Volume13
Issue number2
DOIs
Publication statusPublished - Feb 2018

Keywords

  • Malignant Pleural Mesothelioma
  • Y-box binding protein-1
  • YBX1
  • miR-137
  • microRNA
  • Cancer
  • Malignant pleural mesothelioma

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