Jia Mengxian, Zhang Wenbin, Zhu Junle, Huang Changgang, Zhou Jian, Lian Jiashu, Wang Ying, Teng Honglin, Huang Zhihui
College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, China.
Department of Orthopedics (Spine Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Front Oncol. 2021 Aug 4;11:685893. doi: 10.3389/fonc.2021.685893. eCollection 2021.
Glioblastoma multiforme (GBM) is one of the deadliest cancers in brain. There have been few treatment advances for GBM despite increasing scientific understanding of this disease. β-hexosaminidase (Hex) is an important enzyme system in human body, encoded by two genes, and , are closely related to central nervous system (CNS) diseases such as Sandhoff disease (SD) and Tay-Sachs disease (TSD). However, the expression pattern and function of HEXA and HEXB in GBM remains unclear. Here, we found that both the mRNA and protein expression levels of HEXA and HEXB were significantly upregulated in GBM patient samples. The results from single-cell RNA-sequencing (scRNA-seq) database and double immunostaining showed that HEXA and HEXB were specifically expressed in microglia in GBM patient samples. Furthermore, our experiments revealed that conditioned media from and knockdown-microglia cells could inhibit the proliferation and migration of GBM cells. Finally, according to survival analysis based on online database, higher expression of and was associated with poor prognosis in GBM patients. In conclusion, these results suggest that microglial and play fundamental role in GBM progression, and they will be potential biomarkers for GBM.
多形性胶质母细胞瘤(GBM)是脑内最致命的癌症之一。尽管对这种疾病的科学认识不断增加,但GBM的治疗进展却很少。β-己糖胺酶(Hex)是人体中的一种重要酶系统,由两个基因编码,与诸如桑德霍夫病(SD)和泰-萨克斯病(TSD)等中枢神经系统(CNS)疾病密切相关。然而,HEXA和HEXB在GBM中的表达模式和功能仍不清楚。在此,我们发现GBM患者样本中HEXA和HEXB的mRNA和蛋白表达水平均显著上调。单细胞RNA测序(scRNA-seq)数据库和双重免疫染色结果表明,HEXA和HEXB在GBM患者样本的小胶质细胞中特异性表达。此外,我们的实验表明,来自HEXA和HEXB敲低的小胶质细胞的条件培养基可抑制GBM细胞的增殖和迁移。最后,根据基于在线数据库的生存分析,HEXA和HEXB的高表达与GBM患者的不良预后相关。总之,这些结果表明小胶质细胞的HEXA和HEXB在GBM进展中起重要作用,并且它们将成为GBM的潜在生物标志物。