microRNAs are differentially regulated between MDM2-positive and negative malignant pleural mesothelioma
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Robert Fred Henry Walter1,2, Claudia Vollbrecht3,4, Robert Werner2, Jeremias Wohlschlaeger2, Daniel Christian Christoph5, Kurt Werner Schmid2, Fabian Dominik Mairinger2,4
1Ruhrlandklinik, West German Lung Centre, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
2Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
3Institute of Pathology, University Hospital Cologne, Köln, Germany
4Institute of Pathology, Division of Molecular Pathology, Charité, Berlin, Germany
5Department of Medical Oncology, West German Cancer Centre, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Fabian Dominik Mairinger, e-mail: firstname.lastname@example.org
Keywords: MDM2, microRNA, pleural mesothelioma, NanoString nCounter
Received: September 04, 2015 Accepted: February 02, 2016 Published: February 24, 2016
Background: Malignant pleural mesothelioma (MPM) is a highly aggressive tumour first-line treated with a combination of cisplatin and pemetrexed. MDM2 and P14/ARF (CDKN2A) are upstream regulators of TP53 and may contribute to its inactivation. In the present study, we now aimed to define the impact of miRNA expression on this mechanism.
Material and Methods: 24 formalin-fixed paraffin-embedded (FFPE) tumour specimens were used for miRNA expression analysis of the 800 most important miRNAs using the nCounter technique (NanoString). Significantly deregulated miRNAs were identified before a KEGG-pathway analysis was performed.
Results: 17 miRNAs regulating TP53, 18 miRNAs regulating MDM2, and 11 miRNAs directly regulating CDKN2A are significantly downregulated in MDM2-expressing mesotheliomas. TP53 is downregulated in MDM2-negative tumours through miRNAs with a miSVR prediction score of 11.67, RB1 with a prediction score of 8.02, MDM2 with a prediction score of 4.50 and CDKN2A with a prediction score of 1.27.
Conclusion: MDM2 expression seems to impact miRNA expression levels in MPM. Especially, miRNAs involved in TP53-signaling are strongly decreased in MDM2-positive mesotheliomas. A better understanding of its tumour biology may open the chance for new therapeutic approaches and thereby augment patients’ outcome.
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