Dataset Information

MicroRNAs are differentially regulated between MDM2-positive and negative malignant pleural mesothelioma.

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.

SUBMITTER: Walter RF

PROVIDER: S-EPMC4951323 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Publications

microRNAs are differentially regulated between MDM2-positive and negative malignant pleural mesothelioma.

Walter Robert Fred Henry RF Vollbrecht Claudia C Werner Robert R Wohlschlaeger Jeremias J Christoph Daniel Christian DC Schmid Kurt Werner KW Mairinger Fabian Dominik FD

Oncotarget 20160401 14

<h4>Background</h4>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.<h4>Material and methods</h4>24 formalin-fixed paraffin-embedded (FFPE) tumour specimens were used for miRNA expression analysis of the 800 most important ...[more]

PMID: 26918730

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