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Status |
Public on Oct 08, 2019 |
Title |
Non-oncogene addiction to SIRT3 plays a critical role in lymphomagenesis |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Diffuse large B-cell lymphomas (DLBCLs) are genetically heterogeneous and highly proliferative neoplasms derived from germinal center (GC) B-cells. Herein, we show that DLBCLs are dependent on mitochondrial lysine deacetylase SIRT3 for proliferation, survival, self-renewal, and tumor growth in vivo regardless of disease subtype and genetics. SIRT3 knockout attenuated B-cell lymphomagenesis in VavP-Bcl2 mice without affecting normal GC formation. Mechanistically, SIRT3 depletion impaired glutamine flux to the TCA cycle via glutamate dehydrogenase and reduction in acetyl-CoA pools, which in turn induce autophagy and cell death. We developed a mitochondrial-targeted Class I sirtuin inhibitor, YC8-02, that phenocopied the effects of SIRT3 depletion and killed DLBCL cells. SIRT3 is thus a metabolic non-oncogene addiction and therapeutic target for DLBCLs.
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Overall design |
RNAseq results of SIRT3 expression in DLBCL
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Contributor(s) |
Li M, Teater M, Melnick AM |
Citation(s) |
31185214 |
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Submission date |
May 06, 2019 |
Last update date |
Oct 11, 2019 |
Contact name |
Matt Teater |
E-mail(s) |
mrt2001@med.cornell.edu
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Organization name |
Weill Cornell Medical College
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Street address |
445 E 69th St
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City |
New York |
State/province |
NY |
ZIP/Postal code |
10021 |
Country |
USA |
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Platforms (1) |
GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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Samples (63)
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Relations |
BioProject |
PRJNA541280 |
SRA |
SRP195537 |