Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China; Department of Urology, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, 510900, China.
Cancer Lett. 2023 Nov 28;579:216464. doi: 10.1016/j.canlet.2023.216464. Epub 2023 Oct 24.
The suppressor of variegation enhancer of zeste-trithorax (SET) domain methyltransferases have been reported to function as key regulators in multiple tumor types by catalyzing histone lysine methylation. Nevertheless, our understanding on the role of these lysine methyltransferases, including SETD4, in prostate cancer (PCa) remains limited. Hence, the specific role of SETD4 in PCa was investigated in this study. The expression of SETD4 in PCa cells and tissue samples was downregulated in PCa cells and tissue specimens, and decreased SETD4 expression led to inferior clinicopathological characteristics in patients with PCa. knockdown of SETD4 facilitated the proliferation of PCa cells and accelerated cell cycle progression. Mechanistically, SETD4 repressed NUPR1 transcription by methylating H3K27 to generate H3K27me3, subsequently inactivated Akt pathway and impeded the tumorigenesis of PCa. Our results highlight that SETD4 prevents the development of PCa by catalyzing the methylation of H3K27 and suppressing NUPR1 transcription, subsequently inactivating the Akt signaling pathway. The findings suggest the potential application of SETD4 in PCa prognosis and therapeutics.
抑制杂色增强子的 SET 域甲基转移酶已被报道通过催化组蛋白赖氨酸甲基化在多种肿瘤类型中作为关键调节剂发挥作用。然而，我们对这些赖氨酸甲基转移酶（包括 SETD4）在前列腺癌（PCa）中的作用的理解仍然有限。因此，本研究旨在研究 SETD4 在 PCa 中的特定作用。在 PCa 细胞和组织样本中，SETD4 的表达在 PCa 细胞和组织标本中下调，并且降低的 SETD4 表达导致 PCa 患者的临床病理特征较差。SETD4 的下调促进了 PCa 细胞的增殖并加速了细胞周期进程。在机制上，SETD4 通过甲基化 H3K27 来抑制 NUPR1 转录，从而产生 H3K27me3，随后失活 Akt 途径并阻碍 PCa 的肿瘤发生。我们的结果表明，SETD4 通过催化 H3K27 的甲基化和抑制 NUPR1 转录来预防 PCa 的发生，从而失活 Akt 信号通路。这些发现表明 SETD4 在 PCa 的预后和治疗中有潜在的应用。
