Methylation Status of the Nanog Promoter Determines the Switch between Cancer Cells and Cancer Stem Cells
Abstract: Cancer stem cells (CSCs) are the main cause of tumor development, metastasis, and relapse. CSCs are thus considered promising targets for cancer therapy. However, it is hard to eradicate CSCs due to their inherent plasticity and heterogeneity, and the underlying mechanism of the switch between non‐CSCs and CSCs remains unclear. Here, it is shown that miR‐135a combined with SMYD4 activates Nanog expression and induces the switch of non‐CSCs into CSCs. The miR‐135a level, once elevated, lowers the methylation level of the CG5 site in the Nanog promoter by directly targeting DNMT1. SMYD4 binds to the unmethylated Nanog promoter to activate Nanog expression in Nanog‐negative tumor cells. The in vivo regulation of miR‐135a levels could significantly affect both the CSCs proportion and tumor progression. These findings indicate that DNA methylation of the Nanog promoter modulates the switch of non‐CSCs into CSCs under the control of the miRNA‐135 level. In addition, the related pathways, miR‐135a/DNMT1 and SMYD4, involved in these processes are potential targets for CSC‐targeted therapy.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Methylation Status of the Nanog Promoter Determines the Switch between Cancer Cells and Cancer Stem Cells ; volume:7 ; number:5 ; year:2020 ; extent:11
Advanced science ; 7, Heft 5 (2020) (gesamt 11)
- Creator
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Liu, Shupeng
Cheng, Kai
Zhang, Hui
Kong, Ruijiao
Wang, Shuo
Mao, Chuanbin
Liu, Shanrong
- DOI
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10.1002/advs.201903035
- URN
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urn:nbn:de:101:1-2022062410573970190631
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:26 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Liu, Shupeng
- Cheng, Kai
- Zhang, Hui
- Kong, Ruijiao
- Wang, Shuo
- Mao, Chuanbin
- Liu, Shanrong
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