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. 2024 Jun 27;52(13):7740–7760. doi: 10.1093/nar/gkae547

Figure 6.

Figure 6.

OC2 is a direct suppressor of active androgen. (A) The same mCRPC patient specimens showing OC2 activity inversely correlated with DHT, testosterone and androstenedione levels. (B) A graphic summary of UGT2B15 and UGT2B17 regulation of androgen glucuronidation to suppress the AR axis. (C) UGT2B15 and UGT2B17 are highly expressed in patients with high OC2 activity. (D) RNA-seq data showing OC2 overexpression induced UGT2B15/17 upregulation while knockdown of OC2 suppressed expression of both genes. (E) Loss of OC2 binding to the UGT2B15 promoter region when the predicted binding site is mutated. Luciferase reporter system showing OC2 upregulates UGT2B15 and UGT2B17. The luciferase signal with the OC2 binding site mutation was not affected by the OC2 inhibitor. (F) In a cell-free system using surface plasmon resonance, the OC2 DNA binding region exhibited high affinity to the wild-type UGT2B15 promoter while the mutated DNA sequence (90 nM) exhibited no binding signal. (G) Glucuronidation is highly activated in the OC2 OE condition.