Universität zu Köln

Walter, Robert Fred Henry, Vollbrecht, Claudia, Werner, Robert, Wohlschlaeger, Jeremias, Christoph, Daniel Christian, Schmid, Kurt Werner and Mairinger, Fabian Dominik (2016). microRNAs are differentially regulated between MDM2-positive and negative malignant pleural mesothelioma. Oncotarget, 7 (14). S. 18713 - 18722. ORCHARD PARK: IMPACT JOURNALS LLC. ISSN 1949-2553

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Walter, Robert Fred Henry UNSPECIFIED UNSPECIFIED UNSPECIFIED Vollbrecht, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Werner, Robert UNSPECIFIED UNSPECIFIED UNSPECIFIED Wohlschlaeger, Jeremias UNSPECIFIED UNSPECIFIED UNSPECIFIED Christoph, Daniel Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmid, Kurt Werner UNSPECIFIED UNSPECIFIED UNSPECIFIED Mairinger, Fabian Dominik UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-278858
Journal or Publication Title:	Oncotarget
Volume:	7
Number:	14
Page Range:	S. 18713 - 18722
Date:	2016
Publisher:	IMPACT JOURNALS LLC
Place of Publication:	ORCHARD PARK
ISSN:	1949-2553
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PEMETREXED PLUS CARBOPLATIN; NEUROENDOCRINE TUMORS; EMBRYONIC LETHALITY; MUTATIONAL ANALYSIS; EXPRESSION ANALYSIS; RNA EXPRESSION; CELL CARCINOMA; MESSENGER-RNA; DNA-DAMAGE; P53 Multiple languages Oncology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27885