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Published on: December 21, 2019
MicroRNAs dysregulation in human malignant pleural mesothelioma
Veronica Balatti1, Stefania Maniero, Manuela Ferracin
1Department of Morphology and Embryology, Section of Cellular Biology and Molecular Genetics, and Center of Biotechnology, University of Ferrara, Ferrara, Italy.
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.
Insights
Researchers identified specific microRNAs (miRNAs) that are dysregulated in malignant pleural mesothelioma (MPM). These findings suggest miRNAs could serve as biomarkers and therapeutic targets for this aggressive asbestos-related cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer linked to asbestos exposure.
- Current therapies for MPM are ineffective, highlighting the need for novel treatment strategies.
- MicroRNAs (miRNAs) are increasingly recognized for their roles in cancer development, acting as oncogenes or tumor suppressors.
Purpose of the Study:
- To investigate the miRNA expression profile in human normal pleural mesothelial cells (HMCs) and MPM.
- To identify specific miRNAs dysregulated in MPM that could serve as diagnostic markers or therapeutic targets.
Main Methods:
- Comparative analysis of miRNA expression using microarray in five HMCs and five MPM samples.
- Validation of differential miRNA expression through real-time quantitative reverse-transcriptase polymerase chain reaction and Western blotting.
Main Results:
- Microarray profiling revealed significant differences in miRNA expression between MPM and HMCs.
- The oncomiRNA miR 17-92 cluster and its paralogs (e.g., miR-17-5p, miR-18a, miR-19b, miR-20a, miR-92) were markedly upregulated in MPM.
- Additional dysregulated miRNAs, including miR-7, miR-182, miR-214, and miR-497, were identified in MPM.
Conclusions:
- The identified dysregulated miRNAs in MPM align with findings in other solid tumors.
- These miRNAs target gene products involved in cell cycle regulation, suggesting their critical role in MPM development and progression.
- Specific miRNAs show potential as diagnostic markers and therapeutic targets for malignant pleural mesothelioma.
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