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| Status |
Public on Oct 31, 2023 |
| Title |
Metabolic reprogramming of cancer cells by JMJD6-mediated alternative splicing |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Chromosome 17q gain occurs frequently in MYC-driven tumors including high-risk neuroblastoma. However, the biological consequences of this genetic event remain elusive. Here we show that JMJD6, frequently amplified at the chromosome 17q25 locus, is one of the essential genes to neuroblastoma cells that are engaged in pathways of mitochondrial metabolism, RNA processing and protein homeostasis. JMJD6 cooperates with MYC in cellular transformation and promotes cancer cell proliferation and tumor growth. Mechanistically, JMJD6 physically interacts with RNA-processing machinery to regulate the alternative splicing and protein synthesis. Notably, JMJD6 controls the alternative splicing of glutaminase (GLS), kidney-type glutaminase (KGA) and glutaminase C (GAC), a rate-limiting enzyme of glutaminolysis, and, consequently, the central carbon metabolism in neuroblastoma. Our findings indicate that JMJD6 coordinates with MYC in tumorigenesis by regulating cancer-promoting metabolic programs through an alternative pre-mRNA splicing mechanism.
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| Overall design |
Examination of gene expression profile changes with JMJD6 siRNA knockdown.
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| Contributor(s) |
Yang J, Finkelstein D |
| Citation missing |
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| |
| Submission date |
Oct 13, 2021 |
| Last update date |
Oct 31, 2023 |
| Contact name |
JUN YANG |
| E-mail(s) |
jun.yang2@stjude.org
|
| Organization name |
St Jude Children's Research Hospital
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| Department |
Surgery
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| Street address |
262 Danny Thomas Place
|
| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38105 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA771064 |
| SRA |
SRP341254 |
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