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.
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 humancancers, 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 humantumors. 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.
Authors: A Truini; S Coco; A Alama; C Genova; C Sini; M G Dal Bello; G Barletta; E Rijavec; G Burrafato; F Boccardo; F Grossi Journal: Cell Mol Life Sci Date: 2014-02-23 Impact factor: 9.261
Authors: Yue Xu; Ming Zheng; Robert E Merritt; Joseph B Shrager; Heather A Wakelee; Robert A Kratzke; Chuong D Hoang Journal: Chest Date: 2013-11 Impact factor: 9.410
Authors: Fabian Dominik Mairinger; Robert Werner; Elena Flom; Jan Schmeller; Sabrina Borchert; Michael Wessolly; Jeremias Wohlschlaeger; Thomas Hager; Thomas Mairinger; Jens Kollmeier; Daniel Christian Christoph; Kurt Werner Schmid; Robert Fred Henry Walter Journal: Virchows Arch Date: 2017-05-02 Impact factor: 4.064
Authors: Michaela B Kirschner; Yuen Yee Cheng; Nicola J Armstrong; Ruby C Y Lin; Steven C Kao; Anthony Linton; Sonja Klebe; Brian C McCaughan; Nico van Zandwijk; Glen Reid Journal: Mol Oncol Date: 2014-12-02 Impact factor: 6.603