Li Qi, Fan Jinfeng, Zhou Zhiyan, Ma Zhe, Che Zhifei, Wu Yaoxi, Yang Xiangli, Liang Peiyu, Li Haoyong
Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
Department of Urology, TianYou Hospital affiliated to Wuhan University of Science & Technology, Wuhan, Hubei Province, China.
iScience. 2023 Nov 23;26(12):108523. doi: 10.1016/j.isci.2023.108523. eCollection 2023 Dec 15.
Prostate cancer (PCa) is one of the most common malignant diseases of urinary system and has poor prognosis after progression to castration-resistant prostate cancer (CRPC), and increased cytosine methylation heterogeneity is associated with the more aggressive phenotype of PCa cell line. Activation-induced cytidine deaminase (AID) is a multifunctional enzyme and contributes to antibody diversification. However, the dysregulation of AID participates in the progression of multiple diseases and related with certain oncogenes through demethylation. Nevertheless, the role of AID in PCa remains elusive. We observed a significant upregulation of AID expression in PCa samples, which exhibited a negative correlation with E-cadherin expression. Furthermore, AID expression is remarkably higher in CRPC cells than that in HSPC cells, and AID induced the demethylation of CXCL12, which is required to stabilize the Wnt signaling pathway executor β-catenin and EMT procedure. Our study suggests that AID drives CRPC metastasis by demethylation and can be a potential therapeutic target for CRPC.
前列腺癌（PCa）是泌尿系统最常见的恶性疾病之一，进展为去势抵抗性前列腺癌（CRPC）后预后较差，且胞嘧啶甲基化异质性增加与PCa细胞系更具侵袭性的表型相关。激活诱导的胞苷脱氨酶（AID）是一种多功能酶，有助于抗体多样化。然而，AID的失调参与多种疾病的进展，并通过去甲基化与某些癌基因相关。尽管如此，AID在PCa中的作用仍不清楚。我们观察到PCa样本中AID表达显著上调，其与E-钙黏蛋白表达呈负相关。此外，CRPC细胞中AID表达明显高于激素敏感性前列腺癌（HSPC）细胞，且AID诱导CXCL12去甲基化，这是稳定Wnt信号通路执行因子β-连环蛋白和上皮-间质转化（EMT）过程所必需的。我们的研究表明，AID通过去甲基化驱动CRPC转移，并且可能成为CRPC的潜在治疗靶点。
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