MicroRNAs dysregulation in human malignant pleural mesothelioma

Our plain-English summary of MicroRNAs dysregulation in human malignant pleural mesothelioma, by V. Balatti, S. Maniero, M. Ferracin, et al (Journal of Thoracic Oncology, 2011).

The study

• Authors: V. Balatti, S. Maniero, M. Ferracin, A. Veronese, M. Negrini, G. Ferrocci, F. Martini, M.G. Tognon
• Journal: Journal of Thoracic Oncology
• Published: 2011;6(5):844-51
• Cited by: 78 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

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.

In plain English

This laboratory study compared microRNAs, small molecules that help control which genes are active, in malignant pleural mesothelioma cells and normal pleural cells. The authors used five short-term cultures of normal pleural mesothelial cells, grown from biopsies of young patients without cancer in Ferrara, Italy, and five mesothelioma cell lines bought from cell banks. Asbestos exposure was not measured or tested. Microarray testing found 151 microRNAs that differed more than twofold between the two groups. Of these, 22 differed by a statistically significant amount: 14 were higher and 8 were lower in the mesothelioma cells. Members of the miR-17-92 cluster, which the authors describe as linked to cancer development, were markedly higher in the mesothelioma cells. miR-182 and miR-7 were also higher, while miR-214 and miR-497 were lower. A second laboratory test confirmed the differences for four microRNAs. The protein p21, which helps control cell division, was present in the normal cells but absent or reduced in the mesothelioma cells. The authors concluded that specific microRNAs could be key players in mesothelioma development or progression, and they said further studies are needed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) comparison of microRNA expression in mesothelioma cell lines and normal mesothelial cell cultures, using microarrays, with confirmation by RT-qPCR and Western blotting
• Who was studied: Five short-term cultures of normal human pleural mesothelial cells (4N, 6N, 13N, 16N, 26N) from biopsies of young non-cancer patients at the University/Hospital of Ferrara, Italy, and five commercially obtained malignant pleural mesothelioma cell lines (MSTO-211H, MPP-89, IST-MES2, NCI-H2052, NCI-H28)
• Exposure: No asbestos exposure was studied. The comparison was between mesothelioma cells and normal mesothelial cells. Asbestos appears only as background in the introduction.
• Main results:
  • 151 microRNAs showed more than a twofold change in average expression in the mesothelioma cells compared with the normal mesothelial cells
  • Of these 151, 22 microRNAs (14 overexpressed and 8 down-regulated in mesothelioma) showed a statistically significant difference
  • Members of the miR-17-92 cluster were markedly up-regulated in the mesothelioma samples
  • miR-182 was markedly up-regulated in mesothelioma, and miR-7 was also up-regulated
  • miR-497 and miR-214 were down-regulated in the mesothelioma samples
  • RT-qPCR testing of four microRNAs (miR-17-5p, miR-20a and miR-92 up-regulated; miR-497 down-regulated) confirmed the expression differences between mesothelioma and normal cells
  • Whole-genome testing of the same samples showed an inverse correlation between the selected microRNAs and many of their known target genes
  • In Western blotting of two normal cultures and five mesothelioma cell lines, the cell-cycle protein p21 was normally expressed in the normal cells but absent or reduced in the mesothelioma cells. The authors suggested this could be an effect of miR-17-92 cluster up-regulation.
• The authors' conclusion: The authors concluded that specific microRNAs could be key players in the development or progression of malignant pleural mesothelioma. They added that some may be mesothelioma markers and possible targets for new treatments.
• Limitations the authors state:
  • Some target genes did not show the expected change at the mRNA level, which the authors attributed to microRNA action on protein production or to several microRNAs acting on the same target
  • The authors stated that further studies are still needed

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Mesothelial Cells, Tumor Suppressor Gene.

Related studies

• miR-1254 and miR-574-5p: serum-based microRNA biomarkers for early-stage non-small cell lung cancer — K.M. Foss, C. Sima, et al. (2011)
• Circulating microRNAs found dysregulated in ex-exposed asbestos workers and pleural mesothelioma patients as potential new biomarkers — I. Bononi, M. Comar, et al. (2016)
• Downregulated microRNAs in the differential diagnosis of malignant pleural mesothelioma — G.V. Gee, D.C. Koestler, et al. (2010)
• ZIC1 is silenced and has tumor suppressor function in malignant pleural mesothelioma — Y.Y. Cheng, M.B. Kirschner, et al. (2013)
• Integrative analysis of microRNA, mRNA and aCGH data reveals asbestos- and histology-related changes in lung cancer — P. Nymark, M. Guled, et al. (2011)
• A diagnostic assay based on microRNA expression accurately identifies malignant pleural mesothelioma — H. Benjamin, D. Lebanony, et al. (2010)

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