Hypoxia regulates endogenous double-stranded RNA production via reduced mitochondrial DNA transcription
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...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Frontiers
2021
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| _version_ | 1826312328746893312 |
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| author | Arnaiz, E Miar, A Dias Junior, AG Prasad, N Schulze, U Waithe, D Nathan, JA Rehwinkel, J Harris, AL |
| author_facet | Arnaiz, E Miar, A Dias Junior, AG Prasad, N Schulze, U Waithe, D Nathan, JA Rehwinkel, J Harris, AL |
| author_sort | Arnaiz, E |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T08:25:56Z |
| format | Journal article |
| id | oxford-uuid:45dae5a5-bddf-4125-bc7b-ca274882f518 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:25:56Z |
| publishDate | 2021 |
| publisher | Frontiers |
| record_format | dspace |
| spelling | oxford-uuid:45dae5a5-bddf-4125-bc7b-ca274882f5182024-02-20T12:22:45ZHypoxia regulates endogenous double-stranded RNA production via reduced mitochondrial DNA transcriptionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:45dae5a5-bddf-4125-bc7b-ca274882f518EnglishSymplectic ElementsFrontiers2021Arnaiz, EMiar, ADias Junior, AGPrasad, NSchulze, UWaithe, DNathan, JARehwinkel, JHarris, ALHypoxia 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. |
| spellingShingle | Arnaiz, E Miar, A Dias Junior, AG Prasad, N Schulze, U Waithe, D Nathan, JA Rehwinkel, J Harris, AL Hypoxia regulates endogenous double-stranded RNA production via reduced mitochondrial DNA transcription |
| title | Hypoxia regulates endogenous double-stranded RNA production via reduced mitochondrial DNA transcription |
| title_full | Hypoxia regulates endogenous double-stranded RNA production via reduced mitochondrial DNA transcription |
| title_fullStr | Hypoxia regulates endogenous double-stranded RNA production via reduced mitochondrial DNA transcription |
| title_full_unstemmed | Hypoxia regulates endogenous double-stranded RNA production via reduced mitochondrial DNA transcription |
| title_short | Hypoxia regulates endogenous double-stranded RNA production via reduced mitochondrial DNA transcription |
| title_sort | hypoxia regulates endogenous double stranded rna production via reduced mitochondrial dna transcription |
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