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LMAN1 表达的生物信息学分析、临床特征及其对脑胶质瘤细胞增殖和侵袭的影响。

Bioinformatics analysis of LMAN1 expression, clinical characteristics, and its effects on cell proliferation and invasion in glioma.

机构信息

Department of Neurosurgery, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou 225000, China; Central Laboratory, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou 225000, China.

Medical College, Yangzhou University, Yangzhou 225000, China; Department of Pharmacy, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225000, China.

出版信息

Brain Res. 2022 Aug 15;1789:147952. doi: 10.1016/j.brainres.2022.147952. Epub 2022 May 24.

Abstract

Glioma is the most common primary central nervous system malignant tumor with high heterogeneity and poor prognosis. So far, the complex pathological process of glioma has not been fully elucidated, and there is a lack of effective biomarkers for the diagnosis and molecular targeted therapy of glioma. Using bioinformatics methods, 77 upregulated and 89 downregulated differentially expressed genes (DEGs) were detected by intersection analysis in different gene expression datasets of glioma cases from public databases. Then, GO and KEGG pathway analysis revealed that the biological functions of these upregulated DEGs were mainly focused on immune response, and the signaling pathways were mainly enriched in integrin family cell surface interactions. The overexpression of the LMAN1 gene of interest was then confirmed using the TCGA dataset and further verified by qRT-PCR in 29 clinical samples and 5 glioma cell lines. Furthermore, high expression of LMAN1 was found to be associated with higher WHO grade, IDH status, and 1p/19q co-deletion. Survival analysis showed that high expression of LMAN1 was associated with poor prognosis in glioma. Gene set enrichment analysis (GSEA) indicated that many cancer-related pathways were associated with LMAN1-high phenotype. Protein-protein interaction (PPI) analysis revealed significant interaction between LMAN1 and MCFD2, F8, and TMED10. Finally, cell experiments showed that LMAN1 knockdown significantly inhibited the proliferation, migration and invasion and promoted apoptosis in glioma cells. This study highlighted the malignant role of LMAN1 in gliomas and provided a potentially valuable biomarker for prognosis evaluation and molecular targeted therapy of glioma.

摘要

神经胶质瘤是最常见的原发性中枢神经系统恶性肿瘤,具有高度异质性和预后不良。迄今为止,神经胶质瘤的复杂病理过程尚未完全阐明,缺乏有效的生物标志物用于神经胶质瘤的诊断和分子靶向治疗。本研究采用生物信息学方法,通过公共数据库中不同神经胶质瘤病例的基因表达数据集的交集分析,检测到 77 个上调和 89 个下调的差异表达基因(DEGs)。然后,GO 和 KEGG 通路分析显示,这些上调的 DEGs 的生物学功能主要集中在免疫反应上,信号通路主要富集在整合素家族细胞表面相互作用。然后使用 TCGA 数据集证实了感兴趣的 LMAN1 基因的过表达,并在 29 个临床样本和 5 个神经胶质瘤细胞系中通过 qRT-PCR 进一步验证。此外,发现 LMAN1 的高表达与更高的 WHO 分级、IDH 状态和 1p/19q 共缺失有关。生存分析表明,LMAN1 的高表达与神经胶质瘤的不良预后相关。基因集富集分析(GSEA)表明,许多与癌症相关的途径与 LMAN1-高表型相关。蛋白质-蛋白质相互作用(PPI)分析显示 LMAN1 与 MCFD2、F8 和 TMED10 之间存在显著的相互作用。最后,细胞实验表明 LMAN1 敲低显著抑制神经胶质瘤细胞的增殖、迁移和侵袭,并促进细胞凋亡。本研究强调了 LMAN1 在神经胶质瘤中的恶性作用,并为神经胶质瘤的预后评估和分子靶向治疗提供了一个有潜在价值的生物标志物。

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