PDF(Pubmed)
Abstract：
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.
摘要：
积累的数据表明，代谢活性的改变有助于神经胶质瘤的发展。最近,SSADH（琥珀酸半醛脱氢酶）表达的调节，与GABA神经递质的分解代谢有关，被证明会影响神经胶质瘤细胞的特性，如扩散，自我更新和致瘤性。目的探讨SSADH在人脑胶质瘤中表达的临床意义。使用来自神经胶质瘤手术切除的公开单细胞RNA测序数据，我们最初根据ALDH5A1（醛脱氢酶5家族成员A1）的表达对癌细胞进行分组，它编码SSADH。在表达高或低水平ALDH5A1的癌细胞之间差异表达的基因本体论富集分析，强调了与细胞形态发生和运动有关的基因的富集。在胶质母细胞瘤细胞系中，ALDH5A1敲低抑制细胞增殖，诱导细胞凋亡并降低其迁移潜力。这伴随着粘附连接分子ADAM-15的mRNA水平的降低和EMT生物标志物表达的失调。CDH1升高，波形蛋白mRNA水平降低。使用免疫组织化学对95例胶质瘤中的SSADH表达进行评估显示，与正常脑组织相比，癌组织中的SSADH表达显着升高，与临床病理特征无明显相关性。总之,我们的数据表明，无论组织学分级如何，SSADH在神经胶质瘤组织中上调，其表达维持神经胶质瘤细胞的运动。
