Endogenous retrovirus expression activates type-I interferon signaling in an experimental mouse model of mesothelioma development.
Détails
ID Serval
serval:BIB_C3F68222682B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Endogenous retrovirus expression activates type-I interferon signaling in an experimental mouse model of mesothelioma development.
Périodique
Cancer letters
ISSN
1872-7980 (Electronic)
ISSN-L
0304-3835
Statut éditorial
Publié
Date de publication
01/06/2021
Peer-reviewed
Oui
Volume
507
Pages
26-38
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: 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.
Mots-clé
Animals, Asbestos, Crocidolite, Asbestosis/complications, Cell Line, Tumor, DNA Methylation, Disease Models, Animal, Endogenous Retroviruses/genetics, Endogenous Retroviruses/metabolism, Endogenous Retroviruses/pathogenicity, Gene Expression Regulation, Neoplastic, Host-Pathogen Interactions, Interferon Regulatory Factors/genetics, Interferon Regulatory Factors/metabolism, Interferon Type I/genetics, Interferon Type I/metabolism, Mesothelioma/etiology, Mesothelioma/genetics, Mesothelioma/metabolism, Mesothelioma/virology, Mice, Promoter Regions, Genetic, RNA Editing, RNA, Double-Stranded/genetics, RNA, Double-Stranded/metabolism, Signal Transduction, Endogenous retrovirus, Mesothelioma, Type-I interferon Signaling
Pubmed
Web of science
Open Access
Oui
Création de la notice
15/03/2021 10:59
Dernière modification de la notice
27/03/2023 8:32