Cui Chunze, Wu Chunyan, Zhang Shaoqi, Yin Xiaofeng
Department of Neurosurgery, Second Hospital of Shanxi Medical University, Taiyuan, China.
Operating Room, Second Hospital of Shanxi Medical University, Taiyuan, China.
J Cell Mol Med. 2025 Jun;29(11):e70651. doi: 10.1111/jcmm.70651.
A high death rate among glioma patients is primarily due to poor prognostic outcomes and tumour metastasis. Oncolytic viruses have gained attention as a potential therapeutic strategy as eliminating tumour cells and modifying tumour microenvironment. This research highlights the urgent necessity to investigate novel therapeutic targets and clarify molecular mechanisms in glioma. The GSE166914 dataset was analysed to examine the SPP1 and HMOX1 expression after VSV-M51 infection in glioma. By utilising the CancerSEA database, we assessed the potential function of SPP1/HMOX1 among pan-cancer. Analysis of gene/protein expression levels and clinical significance was performed to identify the roles of SPP1/HMOX1 using TCGA-glioma data. A correlation analysis was performed to screen co-expressed genes, followed by GSEA analysis. qPCR and HPA analysis were utilised to assess the mRNA/protein levels of SPP1 and HMOX1 in glioma tissues. The anti-apoptotic activity of SPP1 and HMOX1 was confirmed utilising the CCK-8 assay and flow cytometry. VSV-M51 infection resulted in SPP1/HMOX1 downregulation in T98 cells. The expression levels of SPP1/HMOX1 were significantly increased in glioma and associated with histological classifications and WHO grades. Elevated levels of SPP1/HMOX1 were related to poor prognosis in glioma. SPP1/HMOX1 was involved in influencing glioma cell motility through the PI3K/AKT, JAK-STAT and syndecan 1 signalling pathways. In vitro experiments showed higher expression levels of SPP1/HMOX1 in glioma tissues. Silencing SPP1/HMOX1 suppressed glioma cell proliferation and promoted apoptosis. In conclusion, dysregulated SPP1/HMOX1 expression was strongly related to glioma WHO grades and worse outcomes, providing deeper insights into glioma therapeutic targets and oncolytic virus-based treatments.
胶质瘤患者的高死亡率主要归因于预后不良和肿瘤转移。溶瘤病毒作为一种潜在的治疗策略,因能消除肿瘤细胞和改变肿瘤微环境而受到关注。本研究强调了在胶质瘤中研究新治疗靶点和阐明分子机制的迫切必要性。分析了GSE166914数据集,以检测胶质瘤中VSV-M51感染后SPP1和HMOX1的表达。通过利用CancerSEA数据库,我们评估了SPP1/HMOX1在泛癌中的潜在功能。利用TCGA-胶质瘤数据进行基因/蛋白表达水平分析和临床意义分析,以确定SPP1/HMOX1的作用。进行相关性分析以筛选共表达基因,随后进行GSEA分析。采用qPCR和HPA分析评估胶质瘤组织中SPP1和HMOX1的mRNA/蛋白水平。利用CCK-8试验和流式细胞术证实了SPP1和HMOX1的抗凋亡活性。VSV-M51感染导致T98细胞中SPP1/HMOX1下调。SPP1/HMOX1的表达水平在胶质瘤中显著升高,并与组织学分类和WHO分级相关。SPP1/HMOX1水平升高与胶质瘤预后不良相关。SPP1/HMOX1通过PI3K/AKT、JAK-STAT和syndecan 1信号通路影响胶质瘤细胞的运动。体外实验显示胶质瘤组织中SPP1/HMOX1表达水平较高。沉默SPP1/HMOX1可抑制胶质瘤细胞增殖并促进凋亡。总之,SPP1/HMOX1表达失调与胶质瘤WHO分级及较差预后密切相关,为胶质瘤治疗靶点和基于溶瘤病毒的治疗提供了更深入的见解。