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| Status |
Public on Aug 14, 2020 |
| Title |
Functional genomics of Non-NF2 meningioma development and progression [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Meningiomas are the most common primary brain tumors, where complete surgical resection is often challenging giving rise to recurrence. Mutations of the E3 ubiquitin ligase TRAF7 are found in one-fourth of meningioma patients and typically co-occur with mutations in either KLF4, AKT1, or PI3KCA. By creating an in vitro meningioma model derived from primary meningeal cells, we elucidated the cooperative interactions that conspire meningioma development. A multi-omics framework on meningeal cells revealed TRAF7-mediated rewiring of the proteome with the majority of protein expression being post‐transcriptionally‐regulated. Integrating TRAF7-driven ubiquitinome and proteome alterations and TRAF7 interactome highlight the role of TRAF7 in posttranslational regulation of the cytoskeleton organization. TRAF7 controls actin dynamics by acting as a proteostatic regulator of the RAS-related small GTPases. TRAF7 loss-of-function diminishes ubiquitination of RAS and CDC42, leading to the activation of the PAK and MAPK signaling pathways. Up-regulation of CDC42 signaling promotes anchorage-independent growth of meningeal cells. On the other hand, the RAS/MAPK pathway triggers the tumor suppressive activity of KLF4 that inhibits meningeal cell growth due to the activation of the Semaphorin pathway. Simultaneous loss of KLF4 and TRAF7 function enhances tumorigenic transformation of meningeal cells, functionally confirming their roles in meningioma development.
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| Overall design |
RNA sequencing was performed to identify differentially regulated genes upon expression of different constructs in normal human meningeal cells (HMCs) and mengioma HBL-52 cells
Cells were infected with viral vectors expressing genes of interest and kept in culture
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| Contributor(s) |
Sablina A, Najm P, Zhao P |
| Citation missing |
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| Submission date |
Aug 13, 2020 |
| Last update date |
Aug 16, 2020 |
| Contact name |
Peihua Zhao |
| E-mail(s) |
peihua.zhao@kuleuven.vib.be
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| Organization name |
KU Leuven
|
| Street address |
Herestraat 49
|
| City |
Leuven |
| ZIP/Postal code |
3000 |
| Country |
Belgium |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA657054 |
| SRA |
SRP277427 |
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