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Non-coding RNA regulatory networks in mesothelioma: a narrative review of their implication in innate immune signaling pathways


Felley-Bosco, Emanuela (2021). Non-coding RNA regulatory networks in mesothelioma: a narrative review of their implication in innate immune signaling pathways. Precision Cancer Medicine, 4:23.

Abstract

Malignant mesothelioma is a rare but rapidly fatal disease highly enriched for innate immunity signature in a subset of patients with better clinical outcome. We provide here an overview of current knowledge on RNA regulatory networks altered in mesothelioma and resulting in increased expression of non-coding-RNA ligands stimulating the innate immune system. The focus on non-coding RNA (ncRNA) ligands is dictated by the fact that a large fraction of the non-coding genome is known to be transcribed and forms duplex RNAs able to stimulate anti-viral defense. Hence, we mostly describe double-stranded RNA sensors such as cytosolic RIG-I-like receptors and endosomal leucine-rich receptors Toll-like receptors 3 and their endogenous ligands. The latter include products downstream alteration of alternative splicing, altered RNA processing or expression of repetitive elements induced by demethylation events or deficiency of chromatin remodelers such as histone methyltransferase SETDB1 or histone demethylase KDM1A/LSD1 or inhibition of CDK4/6. Based on knowledge acquired either in experimental pre-clinical models or in clinical trials in other cancers types, all these events are likely to influence the outcome of mesothelioma patients treatment with new modalities which are explored in current mesothelioma clinical trials. Furthermore, immune checkpoint inhibition became recently standard of care in unresectable mesothelioma.

Keywords: Mesothelioma; double-stranded RNA; innate immunity

Abstract

Malignant mesothelioma is a rare but rapidly fatal disease highly enriched for innate immunity signature in a subset of patients with better clinical outcome. We provide here an overview of current knowledge on RNA regulatory networks altered in mesothelioma and resulting in increased expression of non-coding-RNA ligands stimulating the innate immune system. The focus on non-coding RNA (ncRNA) ligands is dictated by the fact that a large fraction of the non-coding genome is known to be transcribed and forms duplex RNAs able to stimulate anti-viral defense. Hence, we mostly describe double-stranded RNA sensors such as cytosolic RIG-I-like receptors and endosomal leucine-rich receptors Toll-like receptors 3 and their endogenous ligands. The latter include products downstream alteration of alternative splicing, altered RNA processing or expression of repetitive elements induced by demethylation events or deficiency of chromatin remodelers such as histone methyltransferase SETDB1 or histone demethylase KDM1A/LSD1 or inhibition of CDK4/6. Based on knowledge acquired either in experimental pre-clinical models or in clinical trials in other cancers types, all these events are likely to influence the outcome of mesothelioma patients treatment with new modalities which are explored in current mesothelioma clinical trials. Furthermore, immune checkpoint inhibition became recently standard of care in unresectable mesothelioma.

Keywords: Mesothelioma; double-stranded RNA; innate immunity

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Additional indexing

Item Type:Journal Article, not_refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Thoracic Surgery
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Oncology
Life Sciences > Cancer Research
Health Sciences > Oncology (nursing)
Health Sciences > Pharmacology (medical)
Health Sciences > Surgery
Health Sciences > Anesthesiology and Pain Medicine
Uncontrolled Keywords:Anesthesiology and Pain Medicine, Pharmacology (medical), Cancer Research, Oncology (nursing), Oncology, Surgery
Language:English
Date:1 September 2021
Deposited On:25 Jan 2022 14:44
Last Modified:22 Dec 2023 08:24
Publisher:AME Publishing Company
ISSN:2617-2216
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.21037/pcm-21-4
  • Content: Published Version
  • Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)