Spine Center, Sanbo Brain Hospital, Capital Medical University, Beijing, China.
Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Int J Immunopathol Pharmacol. 2024 Jan-Dec;38:3946320241276336. doi: 10.1177/03946320241276336.
Spinal cord glioma (SCG), a rare subset of central nervous system (CNS) glioma, represents a complex challenge in neuro-oncology. There has been research showing that Retinol Dehydrogenase 10 (RDH10) may be a tumor promoting factor in brain glioma, but the biological effects of RDH10 remain undefined in SCG. We performed gene set enrichment analysis (GSEA) and unsupervised clustering analysis to investigate the roles of EMT (epithelial-mesenchymal transition) in glioma. DEG (differently expressed gene) screening and correlation analysis were conducted to filter the candidate genes which were closely associated with EMT process in SCG. Enrichment analysis and GSVA (Gene Set Variation Analysis) were conducted to investigate the potential mechanism of RDH10 for SCG. Trans-well and healing assay were performed to explore the role of RDH10 in the invasion of SCG. Western blotting was performed to evaluate the levels of markers in PI3K-AKT and EMT pathway. In vivo tests were conducted to verify the role of RDH10 in EMT process. Bioinformatic analysis demonstrated the EMT pathway was associated with dismal prognosis of glioma. Further analysis demonstrated that RDH10 showed the strongest correlation with the EMT process. Retinol Dehydrogenase 10 expression was significantly increased in SCG tissues, correlating with advanced tumor grade and unfavorable prognosis. Functional analysis indicated that decreasing RDH10 levels impeded the invasive and migratory abilities of SCG cells, whereas increasing RDH10 levels augmented them. Enrichment analysis and western blot revealed that RDH10 regulated EMT process of SCG by PI3K-AKT pathway. We observed that the enhanced invasion ability and increased EMT-related protein induced by RDH10 overexpression can be suppressed by PI3K-AKT pathway inhibitor (LY294002). Our research found that RDH10 was an effective biomarker associated with tumor grade and prognosis of SCG. RDH10 could regulate EMT process of SCG through PI3K-AKT pathway.
脊髓神经胶质瘤(SCG)是中枢神经系统(CNS)神经胶质瘤的一个罕见亚型,是神经肿瘤学中的一个复杂挑战。有研究表明视黄醇脱氢酶 10(RDH10)可能是脑胶质瘤的肿瘤促进因子,但 RDH10 在 SCG 中的生物学效应尚不清楚。我们进行了基因集富集分析(GSEA)和无监督聚类分析,以研究 EMT(上皮-间充质转化)在神经胶质瘤中的作用。进行差异表达基因(DEG)筛选和相关性分析,以筛选与 SCG 中 EMT 过程密切相关的候选基因。进行富集分析和 GSVA(基因集变异分析),以研究 RDH10 对 SCG 的潜在机制。进行 Trans-well 和愈合实验,以探索 RDH10 在 SCG 侵袭中的作用。进行 Western blot 实验,以评估 PI3K-AKT 和 EMT 通路中的标记物水平。进行体内实验,以验证 RDH10 在 EMT 过程中的作用。生物信息学分析表明 EMT 通路与神经胶质瘤的不良预后相关。进一步分析表明,RDH10 与 EMT 过程相关性最强。RDH10 在 SCG 组织中的表达显著增加,与肿瘤分级较高和预后不良相关。功能分析表明,降低 RDH10 水平可抑制 SCG 细胞的侵袭和迁移能力,而增加 RDH10 水平则增强了它们的能力。富集分析和 Western blot 表明,RDH10 通过 PI3K-AKT 通路调节 SCG 的 EMT 过程。我们观察到,RDH10 过表达引起的侵袭能力增强和 EMT 相关蛋白增加,可以被 PI3K-AKT 通路抑制剂(LY294002)抑制。我们的研究发现,RDH10 是与 SCG 肿瘤分级和预后相关的有效生物标志物。RDH10 可以通过 PI3K-AKT 通路调节 SCG 的 EMT 过程。