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SPTLC1 inhibits cell growth via modulating Akt/FOXO1 pathway in renal cell carcinoma cells
Zhenzhen Kong1, Xinming Guo2, Zhijian Zhao1
1Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangdong Key Laboratory of Urology, Guangzhou Institute of Urology, Guangzhou, China.
Abstract:
Serine palmitoyltransferase long chain-1 (SPTLC1), which is the rate-limiting enzyme for sphingolipid biosynthesis, has been indicated to be essential for carcinoma cell survival and proliferation in recent, but its role in the regulation of renal cell carcinoma (RCC) remains unknown. In the present study, we found that SPTLC1 expression was significantly decreased in RCC tissues compared to non-tumor tissues, and low SPTLC1 expression was associated with poor overall survival of RCC patients. In addition, our results revealed that forced expression of SPTLC1 could significantly inhibit cell growth in vitro and in vivo via, at least in part, modulating Akt/FOXO1 signaling pathway, thus representing a novel role of SPTLC1 in the regulation of tumor growth in RCC for the first time.
Insights
Serine palmitoyltransferase long chain-1 (SPTLC1) is downregulated in renal cell carcinoma (RCC), and its restoration inhibits tumor growth by modulating the Akt/FOXO1 pathway, offering a new therapeutic target for RCC.
Area of Science:
- Biochemistry
- Oncology
- Molecular Biology
Background:
- Sphingolipids are crucial for cell function.
- Serine palmitoyltransferase long chain-1 (SPTLC1) is the rate-limiting enzyme in sphingolipid biosynthesis.
- SPTLC1's role in renal cell carcinoma (RCC) is currently unknown.
Purpose of the Study:
- To investigate the role of SPTLC1 in RCC.
- To determine the association between SPTLC1 expression and patient survival.
- To explore the mechanism by which SPTLC1 affects RCC growth.
Main Methods:
- Analysis of SPTLC1 expression in RCC tissues and non-tumor tissues.
- Correlation analysis between SPTLC1 expression and overall survival.
- In vitro and in vivo experiments involving forced expression of SPTLC1.
- Investigation of the Akt/FOXO1 signaling pathway.
Main Results:
- SPTLC1 expression was significantly decreased in RCC tissues compared to non-tumor tissues.
- Low SPTLC1 expression correlated with poorer overall survival in RCC patients.
- Forced expression of SPTLC1 inhibited RCC cell growth in vitro and in vivo.
- SPTLC1 modulated the Akt/FOXO1 signaling pathway.
Conclusions:
- SPTLC1 plays a significant role in the regulation of RCC tumor growth.
- Reduced SPTLC1 expression is a potential biomarker for poor prognosis in RCC.
- Targeting SPTLC1 may represent a novel therapeutic strategy for RCC.
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