Oncogene:在恶性前列腺癌中HNF1B介导的SLUG抑制受EZH2抑制

2019-11-08 AlexYang MedSci原创

前列腺癌是发达国家最常见的恶性疾病。Zeste基因增强子同源物2(EZH2)(主要的组蛋白H3赖氨酸27甲基转移酶)的过表达与前列腺癌的恶性化有关。然而,它的下游基因和途径仍旧没有很好的建立。 最近,有研究人员阐释了肿瘤抑制子肝细胞核因子1β(HNF1B)是EZH2的直接下游把基因。在前列腺癌细胞系中,EZH2能够结合到HNF1B位点并能够抑制HNF1B的表达。上述结果进一步可以由临床样本中

前列腺癌是发达国家最常见的恶性疾病。Zeste基因增强子同源物2(EZH2)(主要的组蛋白H3赖氨酸27甲基转移酶)的过表达与前列腺癌的恶性化有关。然而,它的下游基因和途径仍旧没有很好的建立。

最近,有研究人员阐释了肿瘤抑制子肝细胞核因子1β(HNF1B)是EZH2的直接下游把基因。在前列腺癌细胞系中,EZH2能够结合到HNF1B位点并能够抑制HNF1B的表达。上述结果进一步可以由临床样本中EZH2和HNF1B表达的负相关关系进一步支持。一致的是,HNF1B表达的恢复能够显著的抑制EZH2调控的过度生长和EMT过程,包括了前列腺癌细胞系的迁移和浸润。同时,研究人员发现HNF1B能够结合到几千个靶基因的启动子上,并能够差异的调控876个基因的表达。研究人员同样鉴定了RBBP7/RbAP46与HNF1B互作,并且该互作关系对HNF1B调控的SLUG表达的抑制和EMT 过程是需要的。重要的是,研究人员还发现了更高水平的HNF1B表达或者与更低的EZH2表达结合能够很好的预测前列腺癌更好的预后。

最后,研究人员指出,他们建立了一个之前在前列腺癌肿低估的EZH2-HNF1B-SLUG途径,同时为HNF1B作为转移性前列腺癌的预后标记提供了证据。

原始出处:

Jianqing Wang, Chenxi He, Peng Gao et al. HNF1B-mediated repression of SLUG is suppressed by EZH2 in aggressive prostate cancer. Oncogene. 21 Oct 2019

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    2020-07-16 cy0324
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    2020-08-23 fusion
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    2020-03-16 ay2000fy
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    2019-11-10 zsyan
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    2019-11-08 misszhang

    前列腺癌相关研究,学习了,谢谢梅斯

    0

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