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Published on: October 27, 2020
NANOG regulates the proliferation of PCSCs via the TGF-β1/SMAD pathway
Changming Liu1, Mingxiong Sheng1, Liheng Lin1
1The Department of Urology, Mindong Hospital Affiliated to Fujian Medical University, Fuan, Fujian 355000, People's Republic of China.
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.
Insights
Nanog homeobox (NANOG) regulates prostate cancer stem cell (PCSC) growth by influencing the TGF-β1/SMAD pathway. This suggests NANOG is a potential therapeutic target for overcoming castration resistance in prostate cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Castration resistance in prostate cancer often leads to mortality.
- Prostate cancer stem cells (PCSCs) are implicated in the development of castration resistance.
- The roles of NANOG and TGF-β1/SMAD signaling in PCSCs are not fully understood.
Purpose of the Study:
- To investigate the effect of NANOG on PCSC proliferation.
- To determine the involvement of the TGF-β1/SMAD signaling pathway in NANOG-mediated PCSC regulation.
Main Methods:
- Isolation of CD44+/CD133+/NANOG+ PCSCs from DU145 cells using flow cytometry.
- Silencing of NANOG using short hairpin RNA (shRNA).
- Assessment of PCSC biological behavior and TGF-β1/SMAD signaling pathway activity.
Main Results:
- NANOG expression suppressed PCSC proliferation and induced apoptosis.
- NANOG inhibited cell cycle progression at the G0/G1 phase.
- Reduction in TGF-β1, p15, and p-SMAD2 expression was observed following NANOG silencing.
Conclusions:
- NANOG positively regulates PCSC growth via the TGF-β1/SMAD signaling pathway.
- NANOG plays a critical role in maintaining PCSC characteristics relevant to castration resistance.
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