Hypoxia Regulates Endogenous Double-Stranded RNA Production via Reduced Mitochondrial DNA Transcription.
Hypoxia Regulates Endogenous Double-Stranded RNA Production via Reduced Mitochondrial DNA Transcription.
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DOI：
10.3389/fonc.2021.779739
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发表时间：
2021
影响因子：
4.7
通讯作者：
Harris AL
中科院分区：
文献类型：
--
作者：
Arnaiz E;Miar A;Dias Junior AG;Prasad N;Schulze U;Waithe D;Nathan JA;Rehwinkel J;Harris AL
缺氧是实体瘤中的常见现象，与癌症的特征密切相关。缺氧会促进局部免疫抑制并下调 I 型干扰素 (IFN) 表达和信号传导，这有助于许多癌症治疗的成功。双链 RNA (dsRNA) 在线粒体转录过程中瞬时产生，可内源性激活 I 型 IFN 通路。我们报告了缺氧对乳腺癌中线粒体 dsRNA (mtdsRNA) 生成的影响。我们发现缺氧下不同细胞系的 dsRNA 产量显着减少。该效应与 HIF1α/2α 无关。 mtdsRNA 负责诱导 I 型 IFN，并在缺氧后显着减少。缺氧期间，线粒体编码的基因表达下调，dsRNA 特异性 J2 抗体结合的 mtdsRNA 减少。这些发现揭示了缺氧诱导的免疫抑制的新机制，可以通过缺氧激活疗法来靶向。
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.
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影响因子：
4.7
作者：
Budhwani M;Mazzieri R;Dolcetti R
通讯作者：
Dolcetti R
影响因子：
21.3
作者：
Giampazolias E;Zunino B;Dhayade S;Bock F;Cloix C;Cao K;Roca A;Lopez J;Ichim G;Proïcs E;Rubio-Patiño C;Fort L;Yatim N;Woodham E;Orozco S;Taraborrelli L;Peltzer N;Lecis D;Machesky L;Walczak H;Albert ML;Milling S;Oberst A;Ricci JE;Ryan KM;Blyth K;Tait SWG
通讯作者：
Tait SWG
影响因子：
5.4
作者：
Hertzog J;Dias Junior AG;Rigby RE;Donald CL;Mayer A;Sezgin E;Song C;Jin B;Hublitz P;Eggeling C;Kohl A;Rehwinkel J
通讯作者：
Rehwinkel J
影响因子：
5.6
作者：
Chiche, Johanna;Rouleau, Matthieu;Mazure, Nathalie M.
通讯作者：
Mazure, Nathalie M.
影响因子：
4.4
作者：
D'Erchia, Anna Maria;Atlante, Anna;Pesole, Graziano
通讯作者：
Pesole, Graziano