Sprouty 1 is associated with stemness and cancer progression in glioblastoma
Seo‐Young Park, Hang Yeon Jeong, Don Carlo Batara, Suk Jun Lee, Jeong‐Yong Cho, Sung-Hak Kim
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.