RNA editing in mesothelioma: a look forward

Our plain-English summary of RNA editing in mesothelioma: a look forward, by A. Hariharan, S. Sun, M. Wipplinger, et al (Open Biology, 2020).

The study

• Authors: A. Hariharan, S. Sun, M. Wipplinger, E. Felley-Bosco
• Journal: Open Biology
• Published: 2020;10(10):200112
• Type of article: Review
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

RNA editing is a post-transcriptional process increasing transcript diversity, thereby regulating different biological processes. We recently observed that mutations resulting from RNA editing due to hydrolytic deamination of adenosine increase during the development of mesothelioma, a rare cancer linked to chronic exposure to asbestos. This review gathers information from the published literature and public data mining to explore several aspects of RNA editing and their possible implications for cancer growth and therapy. We address possible links between RNA editing and particular types of mesothelioma genetic and epigenetic alterations and discuss the relevance of an edited substrate in the context of current chemotherapy or immunotherapy.

In plain English

This article was a review, not a new experiment. The authors gathered published research and searched public cancer databases to explore how RNA editing might relate to mesothelioma. RNA editing is a process in which cells chemically change their RNA after it is made, mainly by enzymes called ADARs. The authors' interest came from their group's earlier study in an animal model of asbestos-induced mesothelioma, in which asbestos increased RNA mutations, most often A to G changes. That earlier work also found that high ADAR2 expression was associated with worse overall survival in The Cancer Genome Atlas (TCGA) mesothelioma data. In their own search of an online editing database, the authors found 394 editing events in a type of repeated genetic element in more than 80 mesothelioma samples. According to the same database, MDM2 messenger RNA was edited in its 3′ untranslated region in all TCGA mesothelioma samples. The authors concluded that RNA editing and ADAR expression represent potential biomarkers and targets for mesothelioma immunotherapy. They noted that most functional studies remain to be performed on this cancer type.

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: Review of published literature, with some analysis of public cancer databases
• Who was studied: Mostly published studies. The authors' own data mining used The Cancer Editome Atlas, which covers TCGA tumor samples, and included more than 80 mesothelioma samples.
• Exposure: No exposure was studied directly. The review discusses asbestos in general as the context (the authors do not specify a fiber type for their own work), including an earlier animal model of asbestos-induced mesothelioma.
• Main results:
  • From the authors' own search of The Cancer Editome Atlas: 394 editing events occurred in Alu elements in 3'-UTR regions in more than 80 mesothelioma samples.
  • According to The Cancer Editome Atlas, the 3' untranslated region (3'-UTR) of MDM2 messenger RNA was edited in all TCGA mesothelioma samples.
  • From the authors' group's earlier animal study (Rehrauer et al. 2018, reference 4), not this review: asbestos increased the levels of RNA mutations, and the most common changes were A to G mutations.
  • From the same earlier animal study (reference 4): Adar1 expression showed a significant 3.9-fold increase in inflamed tissue compared with sham-treated tissue.
  • From an earlier analysis of TCGA mesothelioma data (reference 4): high ADAR2 expression was associated with worst overall survival.
• The authors' conclusion: The authors concluded that ADAR-dependent RNA editing and ADAR expression, through their role in type 1 interferon signalling, represent potential biomarkers and targets for mesothelioma immunotherapy, as has been shown for other cancers.
• Limitations the authors state:
  • Only two studies have examined ADAR editing in mesothelioma, and most functional studies remain to be performed on this cancer type.
  • The increased ADAR2 expression in asbestos-exposed mice and its link to survival are difficult to interpret until additional functional studies are carried out.

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, Chemotherapy, Immunotherapy.

Related studies

• Double-Stranded RNA Structural Elements Holding the Key to Translational Regulation in Cancer: The Case of Editing in RNA-Binding Motif Protein 8A — A. Abukar, M. Wipplinger, et al. (2021)
• ADAR2 Regulates Malignant Behaviour of Mesothelioma Cells Independent of RNA-editing Activity — K.I. Sakata, K. Maeda, et al. (2020)
• Endogenous retrovirus expression activates type-I interferon signaling in an experimental mouse model of mesothelioma development — S. Sun, F. Frontini, et al. (2021)
• How asbestos drives the tissue towards tumors: YAP activation, macrophage and mesothelial precursor recruitment, RNA editing, and somatic mutations — H. Rehrauer, L. Wu, et al. (2018)
• GAS5 long non-coding RNA in malignant pleural mesothelioma — A. Renganathan, J. Kresoja-Rakic, et al. (2014)
• Regulation of calretinin in malignant mesothelioma is mediated by septin 7 binding to the CALB2 promoter — W. Blum, L. Pecze, et al. (2018)

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