Hypoxia Regulates Endogenous Double-Stranded RNA Production
IFN
cancer
dsRNA
hypoxia
mitochondria
Journal
Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867
Informations de publication
Date de publication:
2021
2021
Historique:
received:
19
09
2021
accepted:
05
11
2021
entrez:
13
12
2021
pubmed:
14
12
2021
medline:
14
12
2021
Statut:
epublish
Résumé
Hypoxia is a common phenomenon in solid tumours strongly linked to the hallmarks of cancer. Hypoxia promotes local immunosuppression and downregulates type I interferon (IFN) expression and signalling, which contribute to the success of many cancer therapies. Double-stranded RNA (dsRNA), transiently generated during mitochondrial transcription, endogenously activates the type I IFN pathway. We report the effects of hypoxia on the generation of mitochondrial dsRNA (mtdsRNA) in breast cancer. We found a significant decrease in dsRNA production in different cell lines under hypoxia. This effect was HIF1α/2α-independent. mtdsRNA was responsible for induction of type I IFN and significantly decreased after hypoxia. Mitochondrially encoded gene expression was downregulated and mtdsRNA bound by the dsRNA-specific J2 antibody was decreased during hypoxia. These findings reveal a new mechanism of hypoxia-induced immunosuppression that could be targeted by hypoxia-activated therapies.
Identifiants
pubmed: 34900733
doi: 10.3389/fonc.2021.779739
pmc: PMC8651540
doi:
Types de publication
Journal Article
Langues
eng
Pagination
779739Subventions
Organisme : Cancer Research UK
ID : 11359
Pays : United Kingdom
Informations de copyright
Copyright © 2021 Arnaiz, Miar, Dias Junior, Prasad, Schulze, Waithe, Nathan, Rehwinkel and Harris.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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