视黄醇脱氢酶10通过PI3K/AKT途径促进脊髓胶质瘤的上皮-间质转化

Zijun Zhao, Zihan Song, Zairan Wang, Fan Zhang, Ze Ding, Zongmao Zhao, Liqiang Liu, Tao Fan
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引用次数: 0

摘要

背景:脊髓胶质瘤(SCG)是中枢神经系统(CNS)胶质瘤的一个罕见亚型,是神经肿瘤学中的一个复杂难题。有研究表明,视黄醇脱氢酶 10(RDH10)可能是脑胶质瘤的促瘤因子,但 RDH10 在 SCG 中的生物学效应仍未确定。研究方法我们进行了基因组富集分析(GSEA)和无监督聚类分析,以研究EMT(上皮-间质转化)在脑胶质瘤中的作用。通过DEG(差异表达基因)筛选和相关性分析,筛选出与SCG中EMT过程密切相关的候选基因。通过富集分析和基因组变异分析(GSVA)研究 RDH10 对 SCG 的潜在作用机制。为探讨RDH10在SCG侵袭过程中的作用,进行了跨孔试验和愈合试验。用 Western 印迹法评估 PI3K-AKT 和 EMT 通路标记物的水平。体内试验验证了 RDH10 在 EMT 过程中的作用。结果生物信息学分析表明,EMT通路与胶质瘤的不良预后有关。进一步分析表明,RDH10与EMT过程的相关性最强。视黄醇脱氢酶10在SCG组织中的表达明显增加,与肿瘤晚期分级和预后不良相关。功能分析表明,RDH10水平降低会阻碍SCG细胞的侵袭和迁移能力,而RDH10水平升高则会增强其侵袭和迁移能力。富集分析和Western印迹显示,RDH10通过PI3K-AKT通路调控SCG的EMT过程。我们观察到,PI3K-AKT通路抑制剂(LY294002)可抑制RDH10过表达诱导的侵袭能力增强和EMT相关蛋白的增加。结论我们的研究发现,RDH10是与SCG肿瘤分级和预后相关的有效生物标志物。RDH10可通过PI3K-AKT通路调控SCG的EMT过程。
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Retinol dehydrogenase 10 promotes epithelial-mesenchymal transition in spinal cord gliomas via PI3K/AKT pathway.

Background: 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. Methods: 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. Results: 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). Conclusion: 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.

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来源期刊
International Journal of Immunopathology and Pharmacology
International Journal of Immunopathology and Pharmacology Immunology and Microbiology-Immunology
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0.00%
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88
期刊介绍: International Journal of Immunopathology and Pharmacology is an Open Access peer-reviewed journal publishing original papers describing research in the fields of immunology, pathology and pharmacology. The intention is that the journal should reflect both the experimental and clinical aspects of immunology as well as advances in the understanding of the pathology and pharmacology of the immune system.
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