The castration-resistant prostate cancer-associated SNP rs11067228 facilitates neuroendocrine differentiation through an enhancer-mediated chromatin interaction with SRRM4.

ABSTRACT: Neuroendocrine prostate cancer is an aggressive disease characterized by early metastasis, drug resistance and poor prognosis. Genome-wide association studies (GWAS) previously identified numerous single nucleotide polymorphisms (SNPs) associated with prostate cancer. SNP rs11067228 as a significant variant associated with castration-resistant metastasis (CM) in prostate cancer (PCa). However, mechanisms underlying activity of the rs11067228 risk variant remain unclear. Here, we demonstrated that risk SNP rs11067228 is located in an H3K27ac-enriched active enhancer, and that activity of that region affects castration-resistance and neuroendocrine differentiation in PCa cells. We identified the RNA-splicing factor SRRM4 as a functional target gene as shown in both cell line and xenog

SUBMITTER: Jiang Y 

PROVIDER: S-EPMC12837743 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature