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dc.contributor.authorArnaiz, Esther
dc.contributor.authorMiar, Ana
dc.contributor.authorDias Junior, Antonio Gregorio
dc.contributor.authorPrasad, Naveen
dc.contributor.authorSchulze, Ulrike
dc.contributor.authorWaithe, Dominic
dc.contributor.authorNathan, James
dc.contributor.authorRehwinkel, Jan
dc.contributor.authorHarris, Adrian L
dc.date.accessioned2022-02-09T00:30:25Z
dc.date.available2022-02-09T00:30:25Z
dc.date.issued2021
dc.identifier.issn2234-943X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/333754
dc.description.abstractHypoxia 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.
dc.format.mediumElectronic-eCollection
dc.publisherFrontiers Media SA
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectIFN
dc.subjectcancer
dc.subjectdsRNA
dc.subjecthypoxia
dc.subjectmitochondria
dc.titleHypoxia Regulates Endogenous Double-Stranded RNA Production via Reduced Mitochondrial DNA Transcription.
dc.typeArticle
dc.publisher.departmentDepartment of Medicine
dc.date.updated2022-02-07T15:35:37Z
prism.publicationDate2021
prism.publicationNameFront Oncol
prism.startingPage779739
prism.volume11
dc.identifier.doi10.17863/CAM.81171
dcterms.dateAccepted2021-11-05
rioxxterms.versionofrecord10.3389/fonc.2021.779739
rioxxterms.versionVoR
dc.contributor.orcidNathan, James [0000-0002-0248-1632]
dc.identifier.eissn2234-943X
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (215477/Z/19/Z)
cam.issuedOnline2021-11-24
cam.depositDate2022-02-07
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International