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Sprouty 1 is associated with stemness and cancer progression in glioblastoma
Seo-Young Park1, Hang Yeon Jeong2, Don Carlo Batara1
1Animal Molecular Biochemistry Laboratory, Department of Animal Science, College of Agriculture and Life Sciences, Chonnam National University, Gwangju, the Republic of Korea.
Abstract:
Glioblastoma multiforme (GBM) is the most severe type of human brain tumor, with a poor prognosis and a low survival rate. GBM is composed of a variety of cell types, including glioma stem-like cells (GSCs), which attribute to its therapeutic resistance (Boyd et al., 2020). Sprouty1 (SPRY1) was first identified as a receptor tyrosine kinases (RTK) signaling mediator in a mammalian cell (Christofori, 2003), however, its role in GBM is unknown. Therefore, the goal of this study was to investigate the role of SPRY1 in the stemness and aggressiveness of GSCs. The mRNA expression levels of SPRY1 were confirmed using quantitative reverse transcription PCR (RT-qPCR) in normal human astrocytes (NHA), glioma cells, and glioma stem cells. SPRY1 expression was inhibited in glioma stem cells using small interference RNA (siRNAs) to examine its role in cell proliferation and tumorsphere formation. Bioinformatics analyses were also employed to investigate the association of SPRY1 expression with patient survival, tumor grade, and subtypes publicly available datasets. We demonstrated that SPRY1 is highly expressed in glioma stem cells than in NHA, glioma cells, and differentiated glioma stem cells. siRNA-mediated downregulation of SPRY1 expression decreased the stemness and self-renewal ability in GSC11. Bioinformatics results showed that high SPRY1 expression correlates with poor overall survival in glioma patients. Our findings suggest that SPRY1 contributes to the stemness and aggressiveness of GBM.
Insights
Sprouty1 (SPRY1) promotes stemness and aggressiveness in glioblastoma multiforme (GBM). Inhibiting SPRY1 in glioma stem cells reduced self-renewal, suggesting SPRY1 as a potential therapeutic target for this aggressive brain tumor.
Area of Science:
- Neuro-oncology
- Cancer Stem Cell Biology
- Molecular Oncology
Background:
- Glioblastoma multiforme (GBM) is an aggressive brain tumor with low survival rates.
- Glioma stem-like cells (GSCs) contribute to GBM's therapeutic resistance.
- The role of Sprouty1 (SPRY1) in GBM pathogenesis remains largely unknown.
Purpose of the Study:
- To investigate the role of SPRY1 in the stemness and aggressiveness of GSCs.
- To determine the correlation between SPRY1 expression and patient survival in GBM.
Main Methods:
- Quantitative reverse transcription PCR (RT-qPCR) to measure SPRY1 mRNA expression.
- Small interfering RNA (siRNA) to downregulate SPRY1 in GSCs.
- Bioinformatics analysis of public datasets for survival and tumor characteristics.
Main Results:
- SPRY1 is highly expressed in GSCs compared to normal astrocytes and glioma cells.
- Downregulation of SPRY1 reduced GSC stemness and self-renewal capacity.
- High SPRY1 expression significantly correlates with poor overall survival in glioma patients.
Conclusions:
- SPRY1 plays a crucial role in maintaining the stemness and aggressiveness of GSCs.
- SPRY1 represents a potential therapeutic target for improving GBM treatment outcomes.
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