Park Seo-Young, Jeong Hang Yeon, Batara Don Carlo, Lee Suk Jun, Cho Jeong-Yong, Kim Sung-Hak
Animal Molecular Biochemistry Laboratory, Department of Animal Science, College of Agriculture and Life Sciences, Chonnam National University, Gwangju, the Republic of Korea.
Research Group of Aging Metabolism, Korea Food Research Institute, Wanju, the Republic of Korea.
IBRO Neurosci Rep. 2022 Jul 21;13:120-126. doi: 10.1016/j.ibneur.2022.07.003. eCollection 2022 Dec.
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 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 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 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.
多形性胶质母细胞瘤（GBM）是人类最严重的脑肿瘤类型，预后较差，生存率低。GBM由多种细胞类型组成，包括胶质瘤干细胞样细胞（GSCs），这是其具有治疗抗性的原因（博伊德等人，2020年）。Sprouty1（SPRY1）最初被鉴定为哺乳动物细胞中的受体酪氨酸激酶（RTK）信号传导介质（克里斯托弗里，2003年），然而，其在GBM中的作用尚不清楚。因此，本研究的目的是探讨SPRY1在GSCs干性和侵袭性中的作用。使用定量逆转录PCR（RT-qPCR）在正常人星形胶质细胞（NHA）、胶质瘤细胞和胶质瘤干细胞中确认了 的mRNA表达水平。使用小干扰RNA（siRNAs）抑制胶质瘤干细胞中的SPRY1表达，以研究其在细胞增殖和肿瘤球形成中的作用。还采用生物信息学分析来研究 表达与公开可用数据集中患者生存率、肿瘤分级和亚型的关联。我们证明，与NHA、胶质瘤细胞和分化的胶质瘤干细胞相比，SPRY1在胶质瘤干细胞中高表达。siRNA介导的 表达下调降低了GSC11中的干性和自我更新能力。生物信息学结果表明，SPRY1高表达与胶质瘤患者的总体生存率差相关。我们的研究结果表明，SPRY1有助于GBM的干性和侵袭性。
