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Deregulation of miRNAs in malignant pleural mesothelioma is associated with prognosis and suggests an alteration of cell metabolism

De Santi, Chiara; Melaiu, Ombretta; Bonotti, Alessandra; Cascione, Luciano; Di Leva, Gianpiero; Foddis, Rudy; Cristaudo, Alfonso; Lucchi, Marco; Mora, Marco; Truini, Anna; Tironi, Andrea; Murer, Bruno; Boldorini, Renzo; Cipollini, Monica; Gemignani, Federica; Gasparini, Pierluigi; Mutti, Luciano; Landi, Stefano

Deregulation of miRNAs in malignant pleural mesothelioma is associated with prognosis and suggests an alteration of cell metabolism Thumbnail


Authors

Chiara De Santi

Ombretta Melaiu

Alessandra Bonotti

Luciano Cascione

Rudy Foddis

Alfonso Cristaudo

Marco Lucchi

Marco Mora

Anna Truini

Andrea Tironi

Bruno Murer

Renzo Boldorini

Monica Cipollini

Federica Gemignani

Pierluigi Gasparini

Luciano Mutti

Stefano Landi



Abstract

Malignant pleural mesothelioma (MPM) is an aggressive human cancer and miRNAs can play a key role for this disease. In order to broaden the knowledge in this field, the miRNA expression was investigated in a large series of MPM to discover new pathways helpful in diagnosis, prognosis and therapy. We employed nanoString nCounter system for miRNA profiling on 105 MPM samples and 10 healthy pleura. The analysis was followed by the validation of the most significantly deregulated miRNAs by RT-qPCR in an independent sample set. We identified 63 miRNAs deregulated in a statistically significant way. MiR-185, miR-197, and miR-299 were confirmed differentially expressed, after validation study. In addition, the results of the microarray analysis corroborated previous findings concerning miR-15b-5p, miR-126-3p, and miR-145-5p. Kaplan-Meier curves were used to explore the association between miRNA expression and overall survival (OS) and identified a 2-miRNA prognostic signature (Let-7c-5p and miR-151a-5p) related to hypoxia and energy metabolism respectively. In silico analyses with DIANA-microT-CDS highlighted 5 putative targets in common between two miRNAs. With the present work we showed that the pattern of miRNAs expression is highly deregulated in MPM and that a 2-miRNA signature can be a new useful tool for prognosis in MPM.

Journal Article Type Article
Acceptance Date Apr 19, 2017
Publication Date Jun 9, 2017
Journal Scientific Reports
Print ISSN 2045-2322
Publisher Nature Publishing Group
Volume 7
Article Number ARTN 3140
DOI https://doi.org/10.1038/s41598-017-02694-0
Keywords Adult, Aged, Aged, 80 and over, Cell Hypoxia, Energy Metabolism, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Lung Neoplasms
Male, Mesothelioma, MicroRNAs, Middle Aged, Oligonucleotide Array Sequence Analysis, Progno
Publisher URL http://doi.org/10.1038/s41598-017-02694-0

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