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| Status |
Public on Sep 03, 2020 |
| Title |
Inhibiting DDX3X triggers tumor-intrinsic type I interferon response and enhances anti-tumor immunity |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Accumulating evidence has shown that cellular double-stranded RNAs (dsRNAs) induce antiviral innate immune responses in human normal and malignant cancer cells. However, it is not fully understood how endogenous ‘self’ dsRNA homeostasis is regulated in the cell. Here, we show that an RNA-binding protein, DEAD-box RNA helicase 3X (DDX3X), prevents the aberrant accumulation of cellular dsRNAs. Loss of DDX3X induces dsRNA sensor-mediated type I interferon signaling and innate immune response in breast cancer cells due to abnormal cytoplasmic accumulation of dsRNAs. Dual depletion of DDX3X and a dsRNA-editing protein, ADAR1 synergistically activates the cytosolic dsRNA pathway in breast cancer cell. Moreover, inhibiting DDX3X enhances the antitumor activity by increasing tumor intrinsic-type I interferon response, antigen presentation, and tumor-infiltration of cytotoxic T cells as well as dendritic cells in breast tumors, which may lead to the development of breast cancer therapy by targeting DDX3X in combination with immune checkpoint blockade. To assess the impact of DDX3X on the gene expression in the breast cancer, we stably depleted DDX3X in breast cancer MCF7 cells using a short hairpin RNA (shRNA)-mediated knockdown, and performed a genome-wide transcriptome analysis using a next-generation RNA deep sequencing.
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| Overall design |
The analyses were perfomed on 4 samples of DDX3X-control (shNS) and 5 samples of DDX3X-knockdonwn (shDDX3X) MCF7 cells. Total RNA from cells was extracted and sequenced by the SOLiD sequencing with pair-ended whole transcriptome sequencing.
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| Contributor(s) |
Han C, Kwon J, Choi H |
| Citation missing |
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| Submission date |
Sep 02, 2020 |
| Last update date |
Nov 18, 2020 |
| Contact name |
Hyeongjwa Choi |
| E-mail(s) |
hyeongjwa@gmail.com
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| Organization name |
Georgetown University
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| Department |
Oncology
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| Street address |
3970 Reservoir Road NW
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| City |
Washington |
| State/province |
DC |
| ZIP/Postal code |
20007 |
| Country |
USA |
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| Platforms (1) |
| GPL16288 |
AB 5500xl Genetic Analyzer (Homo sapiens) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA660942 |
| SRA |
SRP279724 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE157323_DDX3X_mRNAseq_results.txt.gz |
1.5 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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