Endogenous retrovirus expression activates type-I interferon signaling in an experimental mouse model of mesothelioma development.
Animals
Asbestos, Crocidolite
Asbestosis
/ complications
Cell Line, Tumor
DNA Methylation
Disease Models, Animal
Endogenous Retroviruses
/ genetics
Gene Expression Regulation, Neoplastic
Host-Pathogen Interactions
Interferon Regulatory Factors
/ genetics
Interferon Type I
/ genetics
Mesothelioma
/ etiology
Mice
Promoter Regions, Genetic
RNA Editing
RNA, Double-Stranded
/ genetics
Signal Transduction
Endogenous retrovirus
Mesothelioma
Type-I interferon Signaling
Journal
Cancer letters
ISSN: 1872-7980
Titre abrégé: Cancer Lett
Pays: Ireland
ID NLM: 7600053
Informations de publication
Date de publication:
01 06 2021
01 06 2021
Historique:
received:
04
11
2020
revised:
23
02
2021
accepted:
03
03
2021
pubmed:
14
3
2021
medline:
21
10
2021
entrez:
13
3
2021
Statut:
ppublish
Résumé
Early events in an experimental model of mesothelioma development include increased levels of editing in double-stranded RNA (dsRNA). We hypothesised that expression of endogenous retroviruses (ERV) contributes to dsRNA formation and type-I interferon signaling. ERV and interferon stimulated genes (ISGs) expression were significantly higher in tumor compared to non-tumor samples. 12 tumor specific ERV ("MesoERV1-12") were identified and verified by qPCR in mouse tissues. "MesoERV1-12" expression was lower in mouse embryonic fibroblasts (MEF) compared to mesothelioma cells. "MesoERV1-12" levels were significantly increased by demethylating agent 5-Aza-2'-deoxycytidine treatment and were accompanied by increased levels of dsRNA and ISGs. Basal ISGs expression was higher in mesothelioma cells compared to MEF and was significantly decreased by JAK inhibitor Ruxolitinib, by blocking Ifnar1 and by silencing Mavs. "MesoERV7" promoter was demethylated in asbestos-exposed compared to sham mice tissue as well as in mesothelioma cells and MEF upon 5-Aza-CdR treatment. These observations uncover novel aspects of asbestos-induced mesothelioma whereby ERV expression increases due to promoter demethylation and is paralleled by increased levels of dsRNA and activation of type-I IFN signaling. These features are important for early diagnosis and therapy.
Identifiants
pubmed: 33713739
pii: S0304-3835(21)00108-7
doi: 10.1016/j.canlet.2021.03.004
pii:
doi:
Substances chimiques
Interferon Regulatory Factors
0
Interferon Type I
0
RNA, Double-Stranded
0
Asbestos, Crocidolite
12001-28-4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
26-38Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.