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| Status |
Public on Feb 04, 2020 |
| Title |
Genome-wide Screening Identifies SFMBT1 as an Oncogenic Driver in Cancer with VHL Loss |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
von Hippel-Lindau (VHL) is a critical tumor suppres- sor in clear cell renal cell carcinomas (ccRCCs). It is important to identify additional therapeutic targets in ccRCC downstream of VHL loss besides hypox- ia-inducible factor 2a (HIF2a). By performing a genome-wide screen, we identified Scm-like with four malignant brain tumor domains 1 (SFMBT1) as a candidate pVHL target. SFMBT1 was considered to be a transcriptional repressor but its role in cancer remains unclear. ccRCC patients with VHL loss-of- function mutations displayed elevated SFMBT1 pro- tein levels. SFMBT1 hydroxylation on Proline residue 651 by EglN1 mediated its ubiquitination and degra- dation governed by pVHL. Depletion of SFMBT1 abolished ccRCC cell proliferation in vitro and in- hibited orthotopic tumor growth in vivo. Integrated analyses of ChIP-seq, RNA-seq, and patient prog- nosis identified sphingosine kinase 1 (SPHK1) as a key SFMBT1 target gene contributing to its onco- genic phenotype. Therefore, the pVHL-SFMBT1- SPHK1 axis serves as a potential therapeutic avenue for ccRCC
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| Overall design |
ChIP-seq for SFMBT1 and input control. RNA-seq for two independent siRNA against SFMBT1, as well as scrambled control, each performed in triplicate.
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| Contributor(s) |
Simon JM, Zhang Q |
| Citation(s) |
32023483 |
| |
| Submission date |
Dec 06, 2019 |
| Last update date |
May 10, 2023 |
| Contact name |
Jeremy Simon |
| E-mail(s) |
jsimon@ds.dfci.harvard.edu, jeremy_simon@med.unc.edu
|
| Organization name |
Dana-Farber Cancer Institute
|
| Department |
Department of Data Science
|
| Street address |
450 Brookline Ave
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
| |
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| Platforms (2) |
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| Samples (11)
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| Relations |
| BioProject |
PRJNA593996 |
| SRA |
SRP234978 |
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