Abstract：
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.
摘要：
据报道，zeste-trithorax（SET）结构域甲基转移酶的杂色增强子抑制剂通过催化组蛋白赖氨酸甲基化在多种肿瘤类型中起关键调节因子的作用。然而，我们对这些赖氨酸甲基转移酶的作用的理解，包括SETD4，在前列腺癌（PCa）中仍然有限。因此，本研究调查了SETD4在PCa中的具体作用.PCa细胞和组织标本中SETD4的表达下调，SETD4表达减少导致PCa患者的临床病理特征较差。SETD4敲低可促进PCa细胞的增殖并加速细胞周期进程.机械上,SETD4通过甲基化H3K27以产生H3K27me3抑制NUPR1转录，随后灭活Akt途径并阻碍PCa的肿瘤发生。我们的结果强调，SETD4通过催化H3K27甲基化和抑制NUPR1转录来阻止PCa的发展。随后使Akt信号通路失活。这些发现表明SETD4在PCa预后和治疗中的潜在应用。
