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| Status |
Public on Oct 08, 2020 |
| Title |
EGFR/Src/Erk-Stabilized YTHDF2 Promotes Cholesterol Dysregulation and Invasive Growth of Glioblastoma [RNA-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Epidermal growth factor receptor (EGFR) signaling is constitutively activated in majority of GBM and is associated with a worse prognosis. Here we show that EGFR is responsible for overexpression of the m6A "reader" YTHDF2 in GBM through the EGFR/Src/ERK signaling pathway. YTHDF2 overexpression clinically correlates with poor glioma patient prognosis. EGFR signaling stabilizes YTHDF2 protein through phosphorylation of YTHDF2 serine 39 and threonine 381 by ERK1/2. YTHDF2 is required for GBM cell proliferation, invasion and tumorigenesis. YTHDF2 facilitates m6A-dependent mRNA decay of LXRA and HIVEP2, both are genes impacting glioma patient survival. YTHDF2 promotes tumorigenesis of GBM cells largely through downregulation of LXRA and HIVEP2. Further, YTHDF2 inhibits LXRA-dependent cholesterol homeostasis in GBM cells. Together, our findings extend the landscape of EGFR downstream circuit, uncover novel function for YTHDF2 in GBM tumorigenesis, and highlight an essential role of RNA m6A methylation in cholesterol homeostasis.
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| Overall design |
Expression profiles were generated from GSC11 human glioblastoma stem cell lines transfected with control or YTHDF2 siRNA, which were collected to extract total RNA, and mRNA sequencing was performed.
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| |
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| Contributor(s) |
Huang S |
| Citation(s) |
33420027 |
| |
| Submission date |
Jan 02, 2020 |
| Last update date |
Jan 26, 2021 |
| Contact name |
Youqiong Ye |
| E-mail(s) |
youqye@gmail.com
|
| Phone |
+8613661565591
|
| Organization name |
Shanghai Jiao Tong University School of Medicine
|
| Street address |
280 Chongqing south road
|
| City |
Shanghai |
| ZIP/Postal code |
200025 |
| Country |
China |
| |
|
| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE142828 |
EGFR/Src/Erk-Stabilized YTHDF2 Promotes Cholesterol Dysregulation and Invasive Growth of Glioblastoma |
|
| Relations |
| BioProject |
PRJNA598564 |
| SRA |
SRP239270 |
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