ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/036/SRR10601436/SRR10601436.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/039/SRR10601439/SRR10601439.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/035/SRR10601435/SRR10601435.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/032/SRR10601432/SRR10601432.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/031/SRR10601431/SRR10601431.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/033/SRR10601433/SRR10601433.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/034/SRR10601434/SRR10601434.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/030/SRR10601430/SRR10601430.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/040/SRR10601440/SRR10601440.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/038/SRR10601438/SRR10601438.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR106/037/SRR10601437/SRR10601437.fastq.gzprimaryOK200GenomicsDepartment of Data Science, Dana-Farber Cancer Institutehttps://www.ebi.ac.uk/ena/browser/view/PRJNA593996Homo sapiensvon 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 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.xref:PubMed:32023483ENAfalseGenome-wide Screening Identifies SFMBT1 as an Oncogenic Driver in Cancer with VHL LossGenome-wide Screening Identifies SFMBT1 as an Oncogenic Driver in Cancer with VHL Loss2025-09-242020-02-06PRJNA593996GSE141577960632023483