Non-Coding Transcript Heterogeneity in Mesothelioma: Insights from Asbestos-Exposed Mice

Our plain-English summary of Non-Coding Transcript Heterogeneity in Mesothelioma: Insights from Asbestos-Exposed Mice, by E. Felley-Bosco, H. Rehrauer (International Journal of Molecular Sciences, 2018).

The study

• Authors: E. Felley-Bosco, H. Rehrauer
• Journal: International Journal of Molecular Sciences
• Published: 2018;19(4)
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Mesothelioma is an aggressive, rapidly fatal cancer and a better understanding of its molecular heterogeneity may help with making more efficient therapeutic strategies. Non-coding RNAs represent a larger part of the transcriptome but their contribution to diseases is not fully understood yet. We used recently obtained RNA-seq data from asbestos-exposed mice and performed data mining of publicly available datasets in order to evaluate how non-coding RNA contribute to mesothelioma heterogeneity. Nine non-coding RNAs are specifically elevated in mesothelioma tumors and contribute to human mesothelioma heterogeneity. Because some of them have known oncogenic properties, this study supports the concept of non-coding RNAs as cancer progenitor genes.

In plain English

This short research communication re-examined gene-activity (RNA-seq) data from the authors' earlier experiment. In that experiment, genetically modified mice (C57Bl/6J Nf2+/−) were exposed eight times to crocidolite (blue asbestos), once every three weeks, or were sham-treated, and were killed 33 weeks after the first exposure. The authors studied non-coding RNAs, which are gene products that do not make proteins. Mouse mesothelioma tumors differed from crocidolite-exposed tissue without tumors in 366 non-protein-coding genes, each changed more than 2-fold. Crocidolite-exposed mice differed from sham mice in 108 such genes. The one most raised in tumors was Fendrr. In tumor samples from nine patients, FENDRR was found in all first samples from patients with epithelioid mesothelioma, but not in one patient with biphasic histology. In public data on 87 human mesothelioma samples, most of the selected non-coding RNAs varied between tumors, and three showed no differences. The authors concluded that these RNAs contribute to human mesothelioma heterogeneity and may point to pathways for precision medicine. They noted that the mice developed only spindeloid tumors, unlike the mostly epithelioid human tumors, and that functional experiments are still 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: Short communication: secondary analysis of RNA-seq data from an earlier mouse asbestos experiment, with laboratory confirmation by quantitative PCR, measurement in patient tumor samples, and mining of public human tumor data (TCGA)
• Who was studied: C57Bl/6J Nf2+/− mice in three groups (sham, crocidolite-exposed, crocidolite-exposed with tumors); tumor samples from nine patients taken at different time points; public TCGA data on 87 MPM samples
• Exposure: Crocidolite (blue asbestos), given eight times at three-week intervals; mice were killed 33 weeks after the first exposure
• Main results:
  • In mice, 366 non-protein-coding genes showed more than 2-fold expression change in tumors compared with crocidolite-exposed tissue, and 108 in crocidolite-exposed compared with sham tissue; 33 genes were found in both comparisons
  • Of 14 selected non-coding RNAs, three (Dio3os, Dubr and Morrbid) were also overexpressed in crocidolite-exposed tissue compared with sham-treated mice
  • In mouse mesothelioma tumors, Fendrr showed the highest upregulation of any non-coding RNA gene; this was confirmed by quantitative PCR
  • In the nine patients, FENDRR was detected in all first tumor samples from patients diagnosed with epithelioid mesothelioma, but not in patient P399, who had biphasic histology
  • In the 87 TCGA human samples, HOXA-AS2, FIRRE and MORRBID showed no differences; the other non-coding RNAs examined contributed to tumor heterogeneity
  • In TCGA samples, DNM3OS was amplified in two patients, and miR214 was amplified as well
  • In TCGA samples, alterations of BAP1 and DIO3OS occurred together significantly (p = 0.024), as did alterations of DUBR and miRlet7b (p = 0.028)
• The authors' conclusion: The authors concluded that they identified non-coding RNAs overexpressed in mesothelioma that contribute to human mesothelioma heterogeneity, and suggested that these may indicate pathways for precision medicine
• Limitations the authors state:
  • The mouse model produced only spindeloid tumors, the opposite of human mesothelioma, where epithelioid types are most frequent
  • The RNA extraction method was not optimal for measuring microRNAs, because it does not preserve very short RNAs
  • The finding that FENDRR deletion fits with epithelioid enrichment rests on a single patient
  • Modeling these RNAs in mice may be difficult because they are conserved at much lower rates than protein-coding genes
  • The authors' hypotheses still need functional experiments to validate them

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma.

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