Role of EZH2 in the growth of prostate cancer stem cells isolated from LNCaP cells.
Role of EZH2 in the growth of prostate cancer stem cells isolated from LNCaP cells.
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EZH2 在从 LNCaP 细胞中分离的前列腺癌干细胞生长中的作用
DOI：
10.3390/ijms140611981
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发表时间：
2013-06-05
影响因子：
5.6
通讯作者：
Xu K
中科院分区：
文献类型：
--
作者：
Li K;Liu C;Zhou B;Bi L;Huang H;Lin T;Xu K
zeste增强子同源物2（EZH2）在胚胎和体干细胞的增殖和分化中发挥着至关重要的作用。然而，EZH2在前列腺癌干细胞（PCSC）中的作用和潜在机制仍然未知。本研究旨在研究EZH2对PCSCs的影响。通过荧光激活细胞分选（FACS）从人前列腺癌细胞系LNcap分离PCSC。比较PCSC和非PCSC之间的EZH2表达。使用siRNA介导的EZH2敲低研究EZH2功能与PCSC生长之间的关联。MTT法检测细胞生长情况，流式细胞仪检测细胞周期和凋亡情况。最后，通过荧光素酶报告基因测定上游途径miRNA水平，并通过逆转录酶-聚合酶链反应检测下游途径循环调节因子。结果显示，与PC-3细胞系相比，LNcap细胞系包含更大比例的CD 44 +/CD 133+细胞。与非PCSC相比，PCSC中EZH2上调。沉默EZH2可抑制细胞生长和细胞周期，促进细胞凋亡。此外，EZH2是PCSC中miR-101的直接靶点，EZH2的mRNA水平与miR-101表达呈负相关，siEZH2抑制细胞周期蛋白E2（细胞周期调节因子）。总之，EZH2对PCSC生长至关重要，部分通过miR-101的负调控和细胞周期蛋白E2的正调控。
Enhancer of zeste homolog 2 (EZH2) plays a crucial role in embryonic and somatic stem cells for their proliferation and differentiation. However, the roles and underlying mechanisms of EZH2 in prostate cancer stem cells (PCSCs) remain unknown. This study aimed to investigate the effects of EZH2 on PCSCs. PCSCs were isolated from the human prostate cancer cell line LNcap by fluorescence activated cell sorting (FACS). EZH2 expression was compared between PCSCs and non-PCSCs. The association between EZH2 function and PCSC growth was investigated using siRNA-mediated knock-down of EZH2. Cell growth was investigated by MTT, cell cycle and apoptosis of PCSCs were explored by flow cytometric analysis. Finally, the upstream pathway miRNA level was determined via a luciferase reporter assay, and the downstream pathway cycle regulators were examined via reverse transcriptase-polymerase chain reaction. The results showed that LNcap cell line comprised a greater proportion of CD44+/CD133+ cells by comparison to the PC-3 cell line. EZH2 was up-regulated in PCSCs compared with non-PCSCs. Silence of EZH2 inhibited cell growth and the cell cycle and promoted the progression of apoptosis. Furthermore, EZH2 was a direct target of miR-101 in PCSCs and EZH2’s mRNA levels were inversely correlated with miR-101 expression and cyclin E2 (a cell-cycle regulator) was suppressed by siEZH2. In conclusion, EZH2 is essential for PCSC growth, partly through a negative regulation by miR-101 and positively regulating cyclin E2.
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影响因子：
50.3
作者：
Chang CJ;Yang JY;Xia W;Chen CT;Xie X;Chao CH;Woodward WA;Hsu JM;Hortobagyi GN;Hung MC
通讯作者：
Hung MC
影响因子：
5.3
作者：
O'Carroll, D;Erhardt, S;Jenuwein, T
通讯作者：
Jenuwein, T
影响因子：
11.5
作者：
Raman, JD;Mongan, NP;Gudas, LJ
通讯作者：
Gudas, LJ
影响因子：
25.7
作者：
Aoki, Ryutaro;Chiba, Tetsuhiro;Iwama, Atsushi
通讯作者：
Iwama, Atsushi
DOI：
10.1016/j.bbadis.2009.02.012
发表时间：
2009-04-01
影响因子：
6.2
作者：
Marian, Calin O.;Shay, Jerry W.
通讯作者：
Shay, Jerry W.