MiR-203 Interplays with Polycomb Repressive Complexes to Regulate the Proliferation of Neural Stem/Progenitor Cells.
MiR-203 Interplays with Polycomb Repressive Complexes to Regulate the Proliferation of Neural Stem/Progenitor Cells.
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MiR-203 与 Polycomb 抑制复合物相互作用调节神经干/祖细胞的增殖
DOI：
10.1016/j.stemcr.2017.05.007
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发表时间：
2017-07-11
影响因子：
5.9
通讯作者：
Liu CM
中科院分区：
文献类型：
--
作者：
Liu PP;Tang GB;Xu YJ;Zeng YQ;Zhang SF;Du HZ;Teng ZQ;Liu CM
多梳抑制复合体1(PrC1)和多梳抑制复合体2(PrC2)是两种不同的多梳蛋白，它们通过染色质修饰来维持特定基因集的稳定沉默。虽然PRC2组分EZH2已被认为是促进神经干细胞/祖细胞(NSPC)增殖的表观遗传调节因子，但控制这一过程的调控网络在很大程度上仍不清楚。在这里，我们证明了miR-203在胚胎和成年NSPC中都被EZH2抑制。MIR-203对NSPC的增殖具有负性调节作用。PRC1组件之一Bmi1是NSPC中miR-203的下游靶标。条件性基因敲除Ezh2导致胚胎和成体NSPC的增殖能力降低。同时，BMI1的异位过表达挽救了因miR-203过表达或EZH2缺乏而导致的NSPC的增殖缺陷。因此，本研究为EZH2-miR-203-BMI1调节轴在NSPC增殖调控中的协同作用提供了证据。在NSPC中，MIR-203被EZH2抑制，MIR-203负向调节NSPC的增殖，Bmi1是NSPC中miR-203的下游靶点，MIR-203是PRC2和PRC1之间的中介，调节NSPC的增殖。在本文中，刘昌梅等人证明miR-203是EZH2和BMI1之间的调节NSPC增殖的中介。由于PcG蛋白和microRNAs通常在许多细胞类型或癌症组织中共表达，这样一个复杂的调控网络可能会引导我们寻找新的疾病治疗策略。
The polycomb repressive complexes 1 (PRC1) and 2 (PRC2) are two distinct polycomb group (PcG) proteins that maintain the stable silencing of specific sets of genes through chromatin modifications. Although the PRC2 component EZH2 has been known as an epigenetic regulator in promoting the proliferation of neural stem/progenitor cells (NSPCs), the regulatory network that controls this process remains largely unknown. Here we show that miR-203 is repressed by EZH2 in both embryonic and adult NSPCs. MiR-203 negatively regulates the proliferation of NSPCs. One of PRC1 components, Bmi1, is a downstream target of miR-203 in NSPCs. Conditional knockout of Ezh2 results in decreased proliferation ability of both embryonic and adult NSPCs. Meanwhile, ectopic overexpression of BMI1 rescues the proliferation defects exhibited by miR-203 overexpression or EZH2 deficiency in NSPCs. Therefore, this study provides evidence for coordinated function of the EZH2-miR-203-BMI1 regulatory axis that regulates the proliferation of NSPCs. MiR-203 is repressed by EZH2 in NSPCs MiR-203 negatively regulates the proliferation of NSPCs Bmi1 is a downstream target of miR-203 in NSPCs MiR-203 is a mediator between PRC2 and PRC1 that modulates the proliferation of NSPCs In this article, Chang-Mei Liu and colleagues show that miR-203 is a mediator between EZH2 and BMI1 that modulates the proliferation of NSPCs. As PcG proteins and microRNAs are usually co-expressed in many cell types or cancer tissues, such a complicated regulatory network might lead us to find new therapeutic strategies for diseases.
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影响因子：
23.9
作者：
Liu C;Teng ZQ;Santistevan NJ;Szulwach KE;Guo W;Jin P;Zhao X
通讯作者：
Zhao X
影响因子：
64.5
作者：
Bonaguidi MA;Wheeler MA;Shapiro JS;Stadel RP;Sun GJ;Ming GL;Song H
通讯作者：
Song H
影响因子：
64.5
作者：
Czermin, B;Melfi, R;Pirrotta, V
通讯作者：
Pirrotta, V
影响因子：
16
作者：
Cao, R;Zhang, Y
通讯作者：
Zhang, Y
影响因子：
10.5
作者：
Liu, Chang-Mei;Wang, Rui-Ying;Zhou, Feng-Quan
通讯作者：
Zhou, Feng-Quan