Journal
JOURNAL OF THORACIC ONCOLOGY
Volume 6, Issue 5, Pages 844-851Publisher
ELSEVIER SCIENCE INC
DOI: 10.1097/JTO.0b013e31820db125
Keywords
MicroRNAs; Microarray; Mesothelioma; Gene target analysis
Categories
Funding
- Fondazione Buzzi UNICEM, Casale Monferrato
- Istituto Superiore per la Prevenzione e la Sicurezza del Lavoro (I.S.P.E.S.L.), Roma
- Emilia Romagna Region, Bologna
- Fondazione Cassa di Risparmio di Cento, Cento
- University of Ferrara, Ferrara, Italy
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Background: Malignant pleural mesothelioma (MPM) is a rare but aggressive asbestos-related cancer that develops by mesothelial cell transformation. At present, there are no effective therapies for MPM. Great efforts have been made in finding specific markers/mechanisms for MPM onset, including studies into microRNAs (miRNAs). Recent studies have shown the differential expression of mature miRNAs in several human cancers, suggesting their potential role as oncogenes or tumor suppressor genes. Methods: In this study, we investigated miRNAs profile in five human normal pleural mesothelial short-term cell cultures (HMCs) and five MPMs, with microarray approach. These results were confirmed by real-time quantitative reverse-transcriptase polymerase chain reaction and Western blotting. Results: A comparative analysis of miRNA expression in MPM and HMCs was carried out. Microarray profiling showed different miRNA expression between MPM and HMCs. Specifically, members of the oncomiRNA miR 17-92 cluster and its paralogs, namely miR 17-5p, 18a, 19b, 20a, 20b, 25, 92, 106a, 106b, were markedly upregulated. Besides, in our investigation, additional miRNAs, such as miR-7, miR-182, miR-214, and miR-497 were found to be dysregulated in MPM. Conclusions: These data are in agreement with results that have previously been reported on dysregulated miRNAs for other solid human tumors. Moreover, in our investigation, additional miRNAs were found to be dysregulated in MPM. Interestingly, gene products that regulate the cell cycle are targets and predicted targets for these miRNAs. Our data suggest that specific miRNAs could be key players in MPM development/progression. In addition, some of these miRNAs may represent MPM markers and potential targets for new therapeutic approaches.
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