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...

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Autores principales:	Esther Arnaiz, Ana Miar, Antonio Gregorio Dias Junior, Naveen Prasad, Ulrike Schulze, Dominic Waithe, James A. Nathan, Jan Rehwinkel, Adrian L. Harris
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	hypoxia IFN dsRNA mitochondria cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/4651a3ea482c498db9341a48c3118d06
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spelling	oai:doaj.org-article:4651a3ea482c498db9341a48c3118d062021-11-30T16:02:11ZHypoxia Regulates Endogenous Double-Stranded RNA Production via Reduced Mitochondrial DNA Transcription2234-943X10.3389/fonc.2021.779739https://doaj.org/article/4651a3ea482c498db9341a48c3118d062021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.779739/fullhttps://doaj.org/toc/2234-943XHypoxia 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.Esther ArnaizEsther ArnaizAna MiarAna MiarAntonio Gregorio Dias JuniorNaveen PrasadUlrike SchulzeDominic WaitheJames A. NathanJan RehwinkelAdrian L. HarrisFrontiers Media S.A.articlehypoxiaIFNdsRNAmitochondriacancerNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hypoxia IFN dsRNA mitochondria cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	hypoxia IFN dsRNA mitochondria cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Esther Arnaiz Esther Arnaiz Ana Miar Ana Miar Antonio Gregorio Dias Junior Naveen Prasad Ulrike Schulze Dominic Waithe James A. Nathan Jan Rehwinkel Adrian L. Harris Hypoxia Regulates Endogenous Double-Stranded RNA Production via Reduced Mitochondrial DNA Transcription
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.
format	article
author	Esther Arnaiz Esther Arnaiz Ana Miar Ana Miar Antonio Gregorio Dias Junior Naveen Prasad Ulrike Schulze Dominic Waithe James A. Nathan Jan Rehwinkel Adrian L. Harris
author_facet	Esther Arnaiz Esther Arnaiz Ana Miar Ana Miar Antonio Gregorio Dias Junior Naveen Prasad Ulrike Schulze Dominic Waithe James A. Nathan Jan Rehwinkel Adrian L. Harris
author_sort	Esther Arnaiz
title	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_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_sort	hypoxia regulates endogenous double-stranded rna production via reduced mitochondrial dna transcription
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/4651a3ea482c498db9341a48c3118d06
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Hypoxia Regulates Endogenous Double-Stranded RNA Production via Reduced Mitochondrial DNA Transcription

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