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

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.

Citation

De Santi, C., Melaiu, O., Bonotti, A., Cascione, L., Di Leva, G., Foddis, R., …Landi, S. (2017). Deregulation of miRNAs in malignant pleural mesothelioma is associated with prognosis and suggests an alteration of cell metabolism. Scientific reports, 7, Article ARTN 3140. https://doi.org/10.1038/s41598-017-02694-0

• 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