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. 2021 Aug 26;9:723676. doi: 10.3389/fcell.2021.723676

FIGURE 5.

FIGURE 5

Potential mechanism of GWAS effects on tumor predisposition. (A) A representative GWAS locus associated with prostate cancer trait affects AR-binding motif predicted by motifbreakR in the enhancer regions. The high-quality AR ChIP-seq data from two independent studies of normal prostate epithelium and prostate cancer cell lines are shown around the representative GWAS locus. (B) rs17694493 is located in the intron of CDKN2B-AS1. AR binds to the SNP and inhibits CDKN2B-AS1. The Pearson correlation of CDKN2B-AS1 expression with AR in the normal prostate is demonstrated in the right panel. The groups harboring the SNP are indicated with a red dot. The anti-correlation was abolished. In the INK4b/ARF/INK4a locus, the effector genes of CDKN2B-AS1 are transcribed to control the cell cycle in the normal prostate tissue. (C) In tumor samples, SNP rs17694493 abolished AR binding and downstream CDKN2B-AS1 inhibition, supported by allelic expression in CPGEA prostate cancer cohorts (right panel). The upregulated expression of CDKN2B-AS1 affected INK4b/ARF/INK4a, gate guard genes of cell cycle.