Epigenetics play an important role in the pathogenesis of prostate cancer; it is urgent to investigate vital transcription factors in methylation regulation with the aim to develop novel treatment strategies targeting prostate cancer. As a member of the zinc finger protein family, REX-1 (reduced expression-1) is a transcription factor that has been reported to be closely linked to the development of several cancers. So far, the expression level and precise function of REX-1 in prostate cancer remain largely unknown. Here, we show that REX-1 was overexpressed in prostate cancer clinical tissues, and its expression level was closely correlated with patient prognosis. REX-1 affected prostate tumor growth in vivo by MEK/ERK phosphorylation. Mechanistic studies indicated that REX-1 recruited DNMT3b (DNA methyltransferase 3b), inhibited the transcription of RASSF1a (RAS association domain family 1a), and further modulated methylation of RASSF1a promoter. Intervention of the REX-1/DNMT3b/RASSF1a axis may shed light on the development of novel therapeutic approaches for prostate cancer treatment. Implications: REX1 overexpression recruits DNMT3b and downregulates RASSF1a by promoter methylation, suggesting that epigenetic intervention may contribute to prostate cancer treatment.

中文翻译：

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REX-1 抑制 RASSF1a 并激活 MEK/ERK 通路以促进前列腺癌的肿瘤发生

表观遗传学在前列腺癌的发病机制中起重要作用；迫切需要研究甲基化调控中的重要转录因子，以开发针对前列腺癌的新治疗策略。作为锌指蛋白家族的成员，REX-1 (reduced expression-1) 是一种转录因子，据报道它与几种癌症的发展密切相关。到目前为止，REX-1 在前列腺癌中的表达水平和精确功能仍然很大程度上未知。在这里，我们显示 REX-1 在前列腺癌临床组织中过表达，其表达水平与患者预后密切相关。REX-1 通过 MEK/ERK 磷酸化影响体内前列腺肿瘤的生长。机制研究表明，REX-1 招募了 DNMT3b（DNA 甲基转移酶 3b），抑制 RASSF1a（RAS 关联结构域家族 1a）的转录，并进一步调节 RASSF1a 启动子的甲基化。REX-1/DNMT3b/RASSF1a 轴的干预可能有助于开发新的前列腺癌治疗方法。启示：REX1 过表达募集 DNMT3b 并通过启动子甲基化下调 RASSF1a，表明表观遗传干预可能有助于前列腺癌的治疗。