Maspin repression is frequently observed in prostate cancer; however, the molecular mechanism(s) causing the loss is not completely understood. Here, we demonstrate that inhibition of class I histone deacetylases (HDACs) mediates re‐expression of maspin which plays an essential role in suppressing proliferation and migration capability in prostate cancer cells. Human prostate cancer LNCaP and DU145 cells treated with HDAC inhibitors, sodium butyrate, and trichostatin A, resulted in maspin re‐expression. Interestingly, an exploration into the molecular mechanisms demonstrates that maspin repression in prostate tumor and human prostate cancer cell lines occurs via epigenetic silencing through an increase in HDAC activity/expression, independent of promoter DNA hypermethylation. Furthermore, transcriptional activation of maspin was accompanied with the suppression of HDAC1 and HDAC8 with significant p53 enrichment at the maspin promoter associated with an increase in histone H3/H4 acetylation. Our results provide evidence of maspin induction as a critical epigenetic event altered by class I HDACs in the restoration of balance to delay proliferation and migration ability of prostate cancer cells.

中文翻译：

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I 类组蛋白去乙酰化酶在前列腺癌 maspin 表达调节中的作用。

在前列腺癌中经常观察到 Maspin 抑制。然而，导致损失的分子机制尚不完全清楚。在这里，我们证明了 I 类组蛋白脱乙酰酶 (HDAC) 的抑制介导了 maspin 的重新表达，maspin 在抑制前列腺癌细胞的增殖和迁移能力中起重要作用。用 HDAC 抑制剂、丁酸钠和曲古抑菌素 A 处理的人前列腺癌 LNCaP 和 DU145 细胞导致 maspin 重新表达。有趣的是，对分子机制的探索表明，前列腺肿瘤和人前列腺癌细胞系中的 maspin 抑制是通过表观遗传沉默通过 HDAC 活性/表达的增加而发生的，独立于启动子 DNA 高甲基化。此外，maspin 的转录激活伴随着 HDAC1 和 HDAC8 的抑制，在与组蛋白 H3/H4 乙酰化增加相关的 maspin 启动子处显着 p53 富集。我们的结果提供了 maspin 诱导作为一种关键的表观遗传事件的证据，该事件被 I 类 HDAC 改变，以恢复平衡以延迟前列腺癌细胞的增殖和迁移能力。