Induction of viral mimicry upon loss of DHX9 and ADAR1 in breast cancer cells.
| العنوان: | Induction of viral mimicry upon loss of DHX9 and ADAR1 in breast cancer cells. |
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| المؤلفون: | Cottrell KA; Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, Saint Louis, Missouri, USA.; ICCE Institute, Washington University School of Medicine, Saint Louis, Missouri, USA.; Department of Biochemistry, Purdue University, West Lafayette, IN, USA., Ryu S; Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, Saint Louis, Missouri, USA.; ICCE Institute, Washington University School of Medicine, Saint Louis, Missouri, USA., Torres LS; Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, Saint Louis, Missouri, USA.; ICCE Institute, Washington University School of Medicine, Saint Louis, Missouri, USA., Schab AM; Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, Saint Louis, Missouri, USA.; ICCE Institute, Washington University School of Medicine, Saint Louis, Missouri, USA., Weber JD; Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, Saint Louis, Missouri, USA.; Department of Cell Biology and Physiology, Washington University School of Medicine, Saint Louis, Missouri, USA.; Department of Biology, Siteman Cancer Center, Washington University School of Medicine, Saint Louis, Missouri, USA.; ICCE Institute, Washington University School of Medicine, Saint Louis, Missouri, USA. |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2023 Oct 31. Date of Electronic Publication: 2023 Oct 31. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | Detection of viral double-stranded RNA (dsRNA) is an important component of innate immunity. However, many endogenous RNAs containing double-stranded regions can be misrecognized and activate innate immunity. The interferon inducible ADAR1-p150 suppresses dsRNA sensing, an essential function for ADAR1 in many cancers, including breast. Although ADAR1-p150 has been well established in this role, the functions of the constitutively expressed ADAR1-p110 isoform are less understood. We used proximity labeling to identify putative ADAR1-p110 interacting proteins in breast cancer cell lines. Of the proteins identified, the RNA helicase DHX9 was of particular interest. Knockdown of DHX9 in ADAR1-dependent cell lines caused cell death and activation of the dsRNA sensor PKR. In ADAR1-independent cell lines, combined knockdown of DHX9 and ADAR1, but neither alone, caused activation of multiple dsRNA sensing pathways leading to a viral mimicry phenotype. Together, these results reveal an important role for DHX9 in suppressing dsRNA sensing by multiple pathways. Competing Interests: The authors declare no potential conflicts of interest. Declaration of interests The authors declare no competing interests. |
| التعليقات: | Update in: Cancer Res Commun. 2024 Apr 4;4(4):986-1003. (PMID: 38530197) |
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| معلومات مُعتمدة: | T32 GM148405 United States GM NIGMS NIH HHS; R25 HG006687 United States HG NHGRI NIH HHS; K99 MD016946 United States MD NIMHD NIH HHS; R01 CA262804 United States CA NCI NIH HHS; R00 MD016946 United States MD NIMHD NIH HHS |
| تواريخ الأحداث: | Date Created: 20230313 Latest Revision: 20240411 |
| رمز التحديث: | 20240411 |
| مُعرف محوري في PubMed: | PMC10002699 |
| DOI: | 10.1101/2023.02.27.530307 |
| PMID: | 36909617 |
| قاعدة البيانات: | MEDLINE |
| DOI: | 10.1101/2023.02.27.530307 |
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