Journal of Thoracic Oncology 2017 November 4 [Epub ahead of print] [Link]
Johnson TG, et. al.,
Malignant pleural mesothelioma (MPM) is an aggressive malignancy linked to asbestos exposure. On a genomic level, MPM is characterised by frequent chromosomal deletions of tumour suppressors, including microRNAs. MiR-137 plays a tumour suppressor role in other cancers, so the aim of this study was to characterise it and its target Y-box binding protein-1 (YB-1) in MPM.
Expression, methylation and copy number status of miR-137 and its host gene MIR137HG were assessed by PCR. Luciferase reporter assays confirmed a direct interaction between miR-137 and YBX1. Cells were transfected with a miR-137 inhibitor, miR-137 mimic and/or YBX1 siRNA, and growth, colony formation, migration and invasion assays were conducted.
MiR-137 expression varied among MPM cell lines and tissue specimens, which was associated with copy number variation and promoter hyper-methylation. High miR-137 expression was linked to poor patient survival. The miR-137 inhibitor did not affect target levels or growth but interestingly, increasing miR-137 levels via mimic transfection suppressed growth, migration and invasion, which was linked to direct YB-1 downregulation. YB-1 was overexpressed in MPM cell lines and inversely correlated with miR-137. RNAi-mediated YB-1 knockdown significantly reduced cell growth, migration and invasion.
MiR-137 can exhibit a tumour-suppressive function in MPM by targeting YB-1. YB-1 knockdown significantly reduces tumour growth, migration and invasion of MPM cells. Therefore, YB-1 represents a potential target for novel MPM treatment strategies.