组蛋白去甲基化酶 JMJD1A 通过激活前列腺癌中的 Snail 促进肿瘤进展,Molecular Cancer Research

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组蛋白去甲基化酶 JMJD1A 通过激活前列腺癌中的 Snail 促进肿瘤进展
Molecular Cancer Research ( IF 4.1 ) Pub Date : 2020-02-04 , DOI: 10.1158/1541-7786.mcr-19-0889
Dong-E Tang ₁ , Yong Dai ₁ , Song-Hui Xu _{1,

2}

Affiliation

组蛋白去甲基化酶 JMJD1A 通过去除 H3K9 中的单甲基和二甲基基团以表观遗传控制基因表达，在精子发生、性别决定、干细胞更新和癌症中发挥关键作用。然而，其在前列腺癌进展中的作用仍不清楚。在这里，我们发现与匹配的正常组织相比，前列腺癌组织中的 JMJD1A 显着升高。前列腺癌细胞中的异位 JMJD1A 表达促进体外增殖、迁移和侵袭，以及体内肿瘤发生；JMJD1A 击倒表现出相反的效果。机械地，我们揭示了 JMJD1A 直接与 Snail 基因启动子相互作用并调节其转录活性，从而在体外和体内促进前列腺癌的进展。此外，我们发现 JMJD1A 通过其特殊启动子区域的 H3K9me1 和 H3K9me2 去甲基化转录激活 Snail 表达。总之，我们的研究揭示了 JMJD1A 通过 Snail 在调节前列腺癌细胞的增殖和进展中发挥重要作用，从而突出 JMJD1A 作为晚期前列腺癌的潜在治疗靶点。启示：我们的研究发现 JMJD1A 通过 Snail 转录激活促进前列腺癌细胞的增殖和进展，从而突出 JMJD1A 作为晚期前列腺癌的潜在治疗靶点。从而突出 JMJD1A 作为晚期前列腺癌的潜在治疗靶点。启示：我们的研究发现 JMJD1A 通过 Snail 转录激活促进前列腺癌细胞的增殖和进展，从而突出 JMJD1A 作为晚期前列腺癌的潜在治疗靶点。从而突出 JMJD1A 作为晚期前列腺癌的潜在治疗靶点。启示：我们的研究发现 JMJD1A 通过 Snail 转录激活促进前列腺癌细胞的增殖和进展，从而突出 JMJD1A 作为晚期前列腺癌的潜在治疗靶点。

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Histone demethylase JMJD1A promotes tumor progression via activating Snail in prostate cancer

The histone demethylase JMJD1A plays a key functional role in spermatogenesis, sex determination, stem cell renewal, and cancer via removing mono- and di-methyl groups from H3K9 to epigenetically control gene expression. However, its role in prostate cancer progression remains unclear. Here, we found JMJD1A was significantly elevated in prostate cancer tissue compared with matched normal tissue. Ectopic JMJD1A expression in prostate cancer cells promoted proliferation, migration, and invasion in vitro, and tumorigenesis in vivo; JMJD1A knockdown exhibited the opposite effects. Mechanically, we revealed that JMJD1A directly interacted with the Snail gene promoter and regulated its transcriptional activity, promoting prostate cancer progression both in vitro and in vivo. Furthermore, we found that JMJD1A transcriptionally activated Snail expression via H3K9me1 and H3K9me2 demethylation at its special promoter region. In summary, our studies reveal JMJD1A plays an important role in regulating proliferation and progression of prostate cancer cells though Snail, and thus highlight JMJD1A as potential therapeutic target for advanced prostate cancer. Implications: Our studies identify that JMJD1A promotes the proliferation and progression of prostate cancer cells through enabling Snail transcriptional activation, and thus highlight JMJD1A as potential therapeutic target for advanced prostate cancer.

更新日期：2020-02-04

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