Histone demethylase PHF8 drives neuroendocrine prostate cancer progression by epigenetically upregulating FOXA2.
Histone demethylase PHF8 drives neuroendocrine prostate cancer progression by epigenetically upregulating FOXA2.
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组蛋白去甲基化酶 PHF8 通过表观遗传上调 FOXA2 驱动神经内分泌前列腺癌进展
DOI：
10.1002/path.5557
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Jiang J
中科院分区：
文献类型：
--
作者：
Liu Q;Pang J;Wang LA;Huang Z;Xu J;Yang X;Xie Q;Huang Y;Tang T;Tong D;Liu G;Wang L;Zhang D;Ma Q;Xiao H;Lan W;Qin J;Jiang J
神经内分泌前列腺癌（NEPC）是去势抵抗性前列腺癌（CRPC）的一种更具侵袭性的亚型。虽然PHF8可以促进前列腺癌细胞增殖，但PHF8是否参与前列腺癌的发生和进展尚不清楚。通过比较有或没有Phf8基因敲除的转基因小鼠前列腺腺癌（TRAMP）小鼠，我们系统地研究了PHF8在前列腺癌发展中的作用。我们发现PHF 8在腺癌的发生和发展中起着最小的作用。然而，PHF 8对于NEPC是必需的，因为不仅PHF 8在NEPC中高表达，而且没有PHF 8的动物也不能发展NEPC。机制上，PHF 8通过去甲基化和去除FOXA 2基因启动子区域上的抑制性组蛋白标记物来转录上调FOXA 2，并且上调的FOXA 2随后调节参与NEPC发育的基因的表达。由于PHF 8和FOXA 2在患者或患者来源的异种移植物的NEPC组织中高度表达，因此PHF 8和FOXA 2的水平可以单独或组合用作NEPC生物标志物，靶向PHF 8或FOXA 2可能是NEPC治疗的潜在治疗策略。版权所有2020作者。病理学杂志由John Wiley & Sons，Ltd.代表大不列颠和爱尔兰病理学会出版。
Neuroendocrine prostate cancer (NEPC) is a more aggressive subtype of castration‐resistant prostate cancer (CRPC). Although it is well established that PHF8 can enhance prostate cancer cell proliferation, whether PHF8 is involved in prostate cancer initiation and progression is relatively unclear. By comparing the transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with or without Phf8 knockout, we systemically examined the role of PHF8 in prostate cancer development. We found that PHF8 plays a minimum role in initiation and progression of adenocarcinoma. However, PHF8 is essential for NEPC because not only is PHF8 highly expressed in NEPC but also animals without Phf8 failed to develop NEPC. Mechanistically, PHF8 transcriptionally upregulates FOXA2 by demethylating and removing the repressive histone markers on the promoter region of the FOXA2 gene, and the upregulated FOXA2 subsequently regulates the expression of genes involved in NEPC development. Since both PHF8 and FOXA2 are highly expressed in NEPC tissues from patients or patient‐derived xenografts, the levels of PHF8 and FOXA2 can either individually or in combination serve as NEPC biomarkers and targeting either PHF8 or FOXA2 could be potential therapeutic strategies for NEPC treatment. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
82.9
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通讯作者：
Demichelis F
影响因子：
50.3
作者：
Qi J;Nakayama K;Cardiff RD;Borowsky AD;Kaul K;Williams R;Krajewski S;Mercola D;Carpenter PM;Bowtell D;Ronai ZA
通讯作者：
Ronai ZA
DOI：
10.1158/1078-0432.ccr-13-3309
发表时间：
2014-06-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Beltran H;Tomlins S;Aparicio A;Arora V;Rickman D;Ayala G;Huang J;True L;Gleave ME;Soule H;Logothetis C;Rubin MA
通讯作者：
Rubin MA
DOI：
10.1073/pnas.92.8.3439
发表时间：
1995-04-11
影响因子：
11.1
作者：
GREENBERG, NM;DEMAYO, F;ROSEN, JM
通讯作者：
ROSEN, JM