The risk SNP rs11067228 promotes prostate cancer drug resistance and neuroendocrine differentiation through 3D chromatin interactions (4C-seq data set)

Genome-wide association studies (GWAS) previously identified the single nucleotide polymorphism (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 active H3K27ac-enriched enhancer, and show that activity of that region affects castration-resistance and neuroendocrine differentiation in PCa cells. We identified 5 functional target genes (UGT2B15, NFASC, TBX3, SRRM4, and HSPA1A) regulated by the risk enhancer and overexpression of the RNA-splicing factor SRRM4 alone was sufficient to induce PCa cell drug resistance and neuroendocrine differentiation.