Combined CRISPRi and proteomics screening reveal a cohesin-CTCF-bound allele contributing to increased expression of RUVBL1 and prostate cancer progression.

ABSTRACT: Genome-wide association studies along with expression quantitative trait loci (eQTL) mapping have identified hundreds of single nucleotide polymorphisms (SNPs) and their target genes in prostate cancer (PCa), yet functional characterization of these risk loci remains challenging. To screen for potential regulatory SNPs, we designed a CRISPRi library containing 9133 guide RNAs (gRNAs) to target 2,166 candidate SNP sites implicated in PCa and identified 117 SNPs that could regulate 90 genes for PCa cell growth advantage. Among these, rs60464856 was covered by multiple gRNAs significantly depleted in the screening (FDR<0.05). Pooled SNP association analysis in the PRACTICAL and FinnGen cohorts showed significantly higher PCa risk for the rs60464856 G allele (pvalue=1.2E-16 and 3.2E-7). Subseq

SUBMITTER: Tian Y 

PROVIDER: S-EPMC9882314 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature