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NANOG通过TGF-β1/SMAD信号通路调控前列腺癌干细胞的增殖。

NANOG regulates the proliferation of PCSCs via the TGF-β1/SMAD pathway.

作者信息

Liu Changming, Sheng Mingxiong, Lin Liheng, Li Huizhang, Guo Shanming, Zhang Jiabin, Chen Guangbing, Chen Huihong

机构信息

The Department of Urology, Mindong Hospital Affiliated to Fujian Medical University, Fuan, Fujian 355000, People's Republic of China.

出版信息

Open Med (Wars). 2020 Sep 1;15(1):841-849. doi: 10.1515/med-2020-0221. eCollection 2020.

Abstract

PURPOSE

In prostate cancer, castration resistance is a factor that frequently leads to death in individuals with this disease. Recent studies have suggested that prostate cancer stem cells (PCSCs) are pivotal regulators in the establishment of castration resistance. The nanog homeobox (NANOG) and the transforming growth factor (TGF)-β1/drosophila mothers against decapentaplegic protein (SMAD) signaling pathways are involved in several cancer stem cells but are not involved in PCSCs. The purpose of this study is to investigate the effect of NANOG on the proliferation of PCSCs regulated by the TGF-β1/SMAD signaling pathway.

METHODS

In this study, we used flow cytometry to isolate CD44+/CD133+/NANOG+ PCSCs from DU145 prostate cancer cells. Then we used short hairpin RNA to silence NANOG and observed the biological behavior and the TGF-β1/SMAD signal of PCSCs.

RESULTS

NANOG decreased PCSC proliferation, increased apoptosis, and blocked cell cycling at G0/G1. Furthermore, reduction in the TGF-β1, p15, and p-SMAD2 expression was observed.

CONCLUSION

These findings suggest that NANOG positively regulates the growth of PCSCs through the TGF-β1/SMAD signaling pathway.

摘要

目的

在前列腺癌中,去势抵抗是导致该病患者死亡的常见因素。最近的研究表明,前列腺癌干细胞(PCSCs)是去势抵抗形成过程中的关键调节因子。纳米盒基因(NANOG)和转化生长因子(TGF)-β1/果蝇抗五聚体蛋白(SMAD)信号通路参与了多种癌症干细胞的相关过程,但不参与前列腺癌干细胞。本研究的目的是探讨NANOG对由TGF-β1/SMAD信号通路调控的前列腺癌干细胞增殖的影响。

方法

在本研究中,我们使用流式细胞术从DU145前列腺癌细胞中分离出CD44+/CD133+/NANOG+前列腺癌干细胞。然后我们使用短发夹RNA沉默NANOG,并观察前列腺癌干细胞的生物学行为和TGF-β1/SMAD信号。

结果

NANOG降低了前列腺癌干细胞的增殖,增加了细胞凋亡,并使细胞周期阻滞在G0/G1期。此外,还观察到TGF-β1、p15和p-SMAD2表达的降低。

结论

这些发现表明,NANOG通过TGF-β1/SMAD信号通路正向调节前列腺癌干细胞的生长。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1703/7712027/e39fd9f8251f/j_med-2020-0221-fig001.jpg

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