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前列腺癌的表观遗传调控

Epigenetic regulation of prostate cancer.

作者信息

Wang Ruixin, Liu Xiaoqi

机构信息

Department of Biochemistry, Purdue University, West Lafayette, IN, 47907, USA.

Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY, 40536, USA.

出版信息

Genes Dis. 2019 Nov 9;7(4):606-613. doi: 10.1016/j.gendis.2019.10.018. eCollection 2020 Dec.

Abstract

Prostate cancer is (PCa) the second leading cause of cancer death in males in the United State, with 174,650 new cases and 31,620 deaths estimated in 2019. It has been documented that epigenetic deregulation such as histone modification and DNA methylation contributes to PCa initiation and progression. EZH2 (enhancer of zeste homolog 2), the catalytic subunit of the Polycomb Repressive Complex (PRC2) responsible for H3K27me3 and gene repression, has been identified as a promising target in PCa. In addition, overexpression of other epigenetic regulators such as DNA methyltransferases (DNMT) is also observed in PCa. These epigenetic regulators undergo extensive post-translational modifications, in particular, phosphorylation. AKT, CDKs, PLK1, PKA, ATR and DNA-PK are the established kinases responsible for phosphorylation of various epigenetic regulators.

摘要

前列腺癌(PCa)是美国男性癌症死亡的第二大主要原因,2019年估计有174,650例新发病例和31,620例死亡。有文献记载,诸如组蛋白修饰和DNA甲基化等表观遗传失调会促使前列腺癌的发生和发展。EZH2(zeste同源物2增强子)是负责H3K27me3和基因抑制的多梳抑制复合物(PRC2)的催化亚基,已被确定为前列腺癌中有前景的靶点。此外,在前列腺癌中还观察到其他表观遗传调节因子如DNA甲基转移酶(DNMT)的过表达。这些表观遗传调节因子会经历广泛的翻译后修饰,尤其是磷酸化。AKT、CDK、PLK1、PKA、ATR和DNA-PK是负责各种表观遗传调节因子磷酸化的既定激酶。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8511/7729106/bc3541f798be/gr1.jpg

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