Combined CRISPRi and Proteomics Screening Reveal a Cohesin-Ctcf-Bound Allele Contributing to Increased Expression of RUVBL1 and Prostate Cancer Progression

Authors

Yijun Tian
Dandan Dong
Zixian Wang
Lang Wu
Jong Y Park
Gong-Hong Wei
Liang Wang

Publication Date

8-3-2023

Journal

American Journal of Human Genetics

Abstract

Genome-wide association studies along with expression quantitative trait locus (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 9,133 guide RNAs (gRNAs) to cover 2,166 candidate SNP loci 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 screening (FDR < 0.05). Pooled SNP association analysis in the PRACTICAL and FinnGen cohorts showed significantly higher PCa risk for the rs60464856 G allele (p value = 1.2 × 10

Keywords

Animals, Humans, Male, Mice, Alleles, ATPases Associated with Diverse Cellular Activities, Carrier Proteins, DNA Helicases, Early Detection of Cancer, Genetic Predisposition to Disease, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Prostate, Prostatic Neoplasms, Proteomics, Cohesins

Comments

Associated Data

PMID: 37541187