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GEO help: Mouse over screen elements for information. |
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Status |
Public on Feb 21, 2023 |
Title |
XRN1 knockdown stimulate innate immune reponse in murine melanoma cells |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing Non-coding RNA profiling by high throughput sequencing
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Summary |
Despite the remarkable achievement of immune checkpoint blockade (ICB) therapy, the response rate is relatively low and only a subset of patients can benefit from the treatment. We hypothesize that targeting RNA decay machinery may lead to accumulation of aberrantRNA, triggering interferon (IFN) signaling and sensitizing tumor cells to immunotherapy. With this in mind, we identified an RNA exoribonuclease, XRN1 as a potential target. Silencing of XRN1 suppressed tumor growth in syngeneic immunocompetent mice and potentiated immunotherapy, while silencing of XRN1 alone did not affect tumor growth in immune deficient mice. Mechanistically, XRN1 depletion activated interferon signaling and viral defense pathway; both pathways play determinant roles in regulating immune evasion. We identified aberrant-RNA sensing signaling proteins (RIG-I/MAVS and PKR) in mediating the expression of IFN genes, as depletion of each of them blunted the elevation of anti-viral/IFN signaling in Xrn1 silenced cells. Analysis of pan-cancer CRISPR screening data indicated that IFN signaling triggered by Xrn1 silencing is a common phenomenon, suggesting that the effect of Xrn1 silencing may be extend to multiple types of cancers.
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Overall design |
XRN1 was knockdown in murine melanoma cell B16/F10 and D4M.3A using multiple techniques including siRNA, shRNA and sgRNA. Five sets of total RNA were extracted; NSG was perfomed to measure the global change of gene expression. The gene expression profiles of XRN1 silenced ones were compared with respective controls (D4M.3A-shXrn1 vs D4M.4A-shCtrl, D4M.3A-sgXrn1 vs D4M.3A-Cas9, B16/F10-siXrn1 vs B16/F10-siCtrl, B16/F10-shXrn1 vs B16/F10-shCtrl, B16/F10-sgXrn1 vs B16/F10-Cas9).
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Contributor(s) |
Ran X, Ding L, Li Y, Yang H |
Citation(s) |
36638333 |
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Submission date |
Mar 30, 2022 |
Last update date |
Feb 21, 2023 |
Contact name |
Ying Li |
E-mail(s) |
csiliyi@nus.edu.sg
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Organization name |
Cancer Science Institute of Singapore
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Street address |
14 Medical Dr, Singapore
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City |
Singapore |
State/province |
--- Select a state --- |
ZIP/Postal code |
117599 |
Country |
Singapore |
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Platforms (2) |
GPL23479 |
BGISEQ-500 (Mus musculus) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (10)
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Relations |
BioProject |
PRJNA821430 |
Supplementary file |
Size |
Download |
File type/resource |
GSE199744_gene.FPKM.txt.gz |
860.1 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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