TR4 Nuclear Receptor Alters the Prostate Cancer CD133+ Stem/Progenitor Cell Invasion via Modulating the EZH2-Related Metastasis Gene Expression.
TR4 Nuclear Receptor Alters the Prostate Cancer CD133+ Stem/Progenitor Cell Invasion via Modulating the EZH2-Related Metastasis Gene Expression.
复制标题
TR4 核受体通过调节 EZH2 相关转移基因表达改变前列腺癌 CD133 干细胞/祖细胞侵袭
DOI：
10.1158/1535-7163.mct-14-0971
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发表时间：
2015-06
影响因子：
5.7
通讯作者：
Chang C
中科院分区：
文献类型：
--
作者：
Zhu J;Yang DR;Sun Y;Qiu X;Chang HC;Li G;Shan Y;Chang C
睾丸核受体4 （TR4）是核受体超家族的一员，介导多种生物学功能，对代谢紊乱和肿瘤进展具有关键影响。本研究表明，TR4可能在前列腺癌（PCa） CD133+干细胞/祖细胞（S/P）侵袭中发挥积极作用。体外和体内用慢病毒沉默RNA靶向TR4可显著抑制PCa CD133+ S/P细胞的侵袭。机制解剖发现，TR4通过结合致癌基因EZH2的5′启动子区转录调控EZH2。靶向TR4抑制EZH2表达的结果可能会抑制其下游关键转移相关基因的表达，包括NOTCH1、TGFβ1、SLUG和MMP9。通过添加EZH2的救援方法逆转tr4介导的PCa S/P细胞侵袭。总之，这些结果表明TR4→EZH2信号通路可能在前列腺癌S/P细胞侵袭中发挥关键作用，并可能使我们开发出更好的治疗前列腺癌转移的方法。
The testicular nuclear receptor 4 (TR4) is a member of the nuclear receptor superfamily that mediates various biological functions with key impacts on metabolic disorders and tumor progression. Here we demonstrate that TR4 may play a positive role in prostate cancer (PCa) CD133+ stem/progenitor (S/P) cell invasion. Targeting TR4 with lentiviral silencing RNA significantly suppressed PCa CD133+ S/P cell invasion both in vitro and in vivo. Mechanism dissection found that TR4 transcriptionally regulates the oncogene EZH2 via binding to its 5′ promoter region. The consequences of targeting TR4 to suppress EZH2 expression may then suppress the expression of its downstream key metastasis-related genes including NOTCH1, TGFβ1, SLUG and MMP9. Rescue approaches via adding the EZH2 reversed the TR4-mediated PCa S/P cell invasion. Together, these results suggest that the TR4→EZH2 signaling may play a critical role in the PCa S/P cell invasion and may allow us to develop a better therapy to battle the PCa metastasis.