Analysis of microRNA expression signatures in malignant pleural mesothelioma, pleural inflammation, and atypical mesothelial hyperplasia reveals common predictive tumorigenesis-related targets

Our plain-English summary of Analysis of microRNA expression signatures in malignant pleural mesothelioma, pleural inflammation, and atypical mesothelial hyperplasia reveals common predictive tumorigenesis-related targets, by E.G. Ramírez-Salazar, L.C. Salinas-Silva, M.E. Vázquez-Manríquez, et al (Experimental and Molecular Pathology, 2014).

The study

• Authors: E.G. Ramírez-Salazar, L.C. Salinas-Silva, M.E. Vázquez-Manríquez, L.V. Gayosso-Gómez, M.C. Negrete-Garcia, S.L. Ramírez-Rodriguez, R. Chávez, E. Zenteno, P. Santillán, J. Kelly-García, B. Ortiz-Quintero
• Journal: Experimental and Molecular Pathology
• Published: 2014;97(3):375-85
• Cited by: 30 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Pleural chronic inflammation (PP) and mesothelial hyperplasia (HP) may be critical to the development of malignant pleural mesothelioma (MPM). Nonetheless, studies searching for mechanistic links involving microRNA (miRNA) regulation among these interrelated processes have not been reported. Using PCR-Array, we identified the miRNAs expressed in pleural tissues diagnosed with MPM (n=5), PP (n=4) and HP (n=5), as well as in non-cancerous/non-inflammatory tissue as the normal control (n=5). We performed bioinformatics and network analysis of differentially expressed miRNAs to identify tumorigenesis-related miRNAs and their biological networks. The targets of four down-regulated miRNAs in MPM (mir-181a-5p, miR-101-3p, miR-145-5p and miR-212-3p), one in PP (mir-101-3p) and one in HP (mir-494) were significantly enriched in "pathways in cancer". Interactome networks revealed that >50% of down-regulated miRNAs in MPM targeted the signaling-activation molecule MAPK1, the transcription factor ETS1 and the mesenchymal transition-associated molecule FZDA, which have been associated with oncogenic function. Comparative analysis revealed that FZD4 was an overlapping gene target of down-regulated miRNAs that were associated with "pathways in cancer" in MPM, PP and HP. Moreover, MAPK1, ETS1 and Cox-2, a pro-inflammatory enzyme associated with over-expression in cancers, were among the 25 overlapping target genes in MPM and PP. This network analysis revealed a potential combinatory effect of deregulated miRNAs in MPM pathogenesis and indicated potential molecular links between pleural inflammation and hyperplasia with tumorigenesis mechanisms in pleura.

Copyright © 2014 Elsevier Inc. All rights reserved.

In plain English

This laboratory study from Mexico measured microRNAs (small pieces of RNA that help regulate gene activity) in archived pleural biopsies from 2009–2010. It compared epithelioid malignant pleural mesothelioma (5 samples), chronic pleural inflammation called pachypleuritis (4) and atypical mesothelial hyperplasia (5) with normal tissue (5). The normal tissue was adjacent noncancerous, noninflammatory tissue from other patients diagnosed with pachypleuritis. Compared with normal tissue, 19 microRNAs differed in mesothelioma (11 lower, 8 higher), 7 in pachypleuritis and 46 in hyperplasia. Computer programs then predicted which genes these microRNAs might control. For four microRNAs that were lower in mesothelioma, the predicted targets were concentrated in cancer-related pathways, and the gene MAPK1 was a predicted target of all four. The gene FZD4 was a predicted target shared by all three conditions. Records noted asbestos exposure for two mesothelioma patients, information the authors said should be considered carefully because it came from nonstandardized questioning. Two pachypleuritis patients also reported exposure. The authors concluded that the results revealed potential molecular links between pleural inflammation, hyperplasia and tumor development, a hypothesis they said must be tested experimentally.

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 study measuring microRNA expression (PCR array) in archived formalin-fixed pleural tissue samples, followed by computer-based prediction of target genes and pathway/network analysis
• Who was studied: Archived pleural biopsies from the Instituto Nacional de Enfermedades Respiratorias "Ismael Cosio Villegas", Mexico, collected 2009–2010. The groups were epithelioid malignant pleural mesothelioma (n = 5), pachypleuritis/chronic inflammation (n = 4), atypical mesothelial hyperplasia (n = 5) and normal control tissue (n = 5). The normal control tissue was adjacent noncancerous, noninflammatory tissue from independent patients diagnosed with pachypleuritis.
• Exposure: Asbestos was not the exposure under study. Clinical records, retrieved retrospectively, noted reported asbestos exposure for 2 of the 5 mesothelioma patients and 2 of the 4 pachypleuritis patients. No fiber type is given.
• Main results:
  • Mesothelioma samples compared with normal tissue: 19 microRNAs were differentially expressed (11 down-regulated, 8 up-regulated), out of 667 tested
  • Pachypleuritis samples compared with normal tissue: 7 microRNAs were differentially expressed (5 down-regulated, 2 up-regulated)
  • Atypical mesothelial hyperplasia samples compared with normal tissue: 46 microRNAs were differentially expressed (4 down-regulated, 42 up-regulated)
  • In mesothelioma, the predicted targets of four down-regulated microRNAs (miR-101-3p, -212-3p, -145-5p and -181a-5p) were enriched in "pathways in cancer"
  • In mesothelioma, MAPK1 was a predicted target of all four of these down-regulated microRNAs; ETS1 and FZD4 were predicted targets of three of them
  • Three predicted target genes of down-regulated microRNAs in cancer pathways were shared by mesothelioma, pachypleuritis and hyperplasia: FZD4, FOXO1 and HHIP
  • Mesothelioma and pachypleuritis shared 25 predicted target genes, including MAPK1, ETS1 and COX-2
• The authors' conclusion: The authors concluded that the results indicate a potential combined effect of deregulated microRNAs in the development of malignant pleural mesothelioma, and potential molecular links between pleural inflammation and hyperplasia and tumor development in the pleura
• Limitations the authors state:
  • The asbestos exposure reported by two mesothelioma patients came from nonstandardized questioning recorded in clinical records and should be considered carefully
  • The study did not confirm the presence of asbestos fibers at the sites of inflammation or hyperplasia
  • The target genes are predictions, and the proposed hypothesis must be tested experimentally

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Inflammation, Atypical Mesothelial Proliferation, Tumorigenesis, Chronic Inflammation, Reactive Mesothelial Hyperplasia, Pleura.

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