累积的数据表明，代谢活动的改变有助于胶质瘤的发展。最近，表达调节降解GABA神经递质的琥珀酸半醛脱氢酶（SSADH）被显示为影响胶质瘤细胞的性质，如增殖、自我更新和肿瘤形成。本研究的目的是调查SSADH在人类胶质瘤中的临床意义。利用胶质瘤手术切除的公共单细胞RNA测序数据，我们首先根据编码SSADH的ALDH5A1（第5家族成员A1醛脱氢酶）表达将癌细胞分组。基因本体富集分析显示，高或低表达ALDH5A1的癌细胞间差异表达的基因涉及细胞形态和运动等方面。在胶质母细胞瘤细胞系中，ALDH5A1的沉默抑制了细胞增殖，诱导了凋亡并降低了它们的迁移潜力。这伴随着紧密连接分子ADAM-15 mRNA水平的降低和EMT生物标志物表达的失调，表明CDH1 mRNA水平增加，而vimentin mRNA水平降低。对95例胶质瘤的免疫组化评估显示，与正常脑组织相比，SSADH表达在癌组织中显著升高，且没有与临床病理特征显著相关。总之，我们的数据表明，SSADH在胶质瘤组织中升高，不论组织学分级如何，其表达支持胶质瘤细胞的运动性。© 2023. 美国实验神经治疗学会。

Accumulating data shows that altered metabolic activity contributes to glioma development. Recently, modulation of SSADH (succinic semialdehyde dehydrogenase) expression, implicated in the catabolism of GABA neurotransmitter, was shown to impact glioma cell properties, such as proliferation, self-renewal and tumorigenicity. The purpose of this study was to investigate the clinical significance of SSADH expression in human gliomas. Using public single-cell RNA-sequencing data from glioma surgical resections, we initially grouped cancer cells according to ALDH5A1 (Aldehyde dehydrogenase 5 family member A1) expression, which encodes SSADH. Gene ontology enrichment analysis of genes differentially expressed between cancer cells expressing high or low levels of ALDH5A1, highlighted enrichment in genes implicated in cell morphogenesis and motility. In glioblastoma cell lines, ALDH5A1 knockdown inhibited cell proliferation, induced apoptosis and reduced their migratory potential. This was accompanied by a reduction in the mRNA levels of the adherens junction molecule ADAM-15 and deregulation in the expression of EMT biomarkers, with increased CDH1 and decreased vimentin mRNA levels. Evaluation of SSADH expression in a cohort of 95 gliomas using immunohistochemistry showed that SSADH expression was significantly elevated in cancer tissues compared to normal brain tissues, without any significant correlation with clinicopathological characteristics. In summary, our data show that SSADH is upregulated in glioma tissues irrespective of the histological grade and its expression sustains glioma cell motility.© 2023. The American Society for Experimental Neurotherapeutics, Inc.