Department of Neurosugery, Lingnan Hospital, branch of The Third Affiliated Hospital of Sun Yat-Sen University, No 2693Kaichuang AvenueHuangpu District, Guangzhou City, Guangdong Province, 510530, People's Republic of China.
Guangzhou BiDa Biological Technology CO., LTD, Guangzhou City, Guangdong Province, 510000, People's Republic of China.
Appl Biochem Biotechnol. 2024 Oct;196(10):6974-6992. doi: 10.1007/s12010-024-04894-7. Epub 2024 Mar 6.
Glioblastoma (GBM) is the most common primary intracranial malignancy with a very low survival rate. Exploring key molecular markers for GBM can help with early diagnosis, prognostic prediction, and recurrence monitoring. This study aims to explore novel biomarkers for GBM via bioinformatics analysis and experimental verification. Dataset GSE103229 was obtained from the GEO database to search differentially expressed lncRNA (DELs), mRNAs (DEMs), and miRNAs (DEMis). Hub genes were selected to establish competing endogenous RNA (ceRNA) networks. The GEPIA database was employed for the survival analysis and expression detection of hub genes. Hub gene expression in GBM tissue samples and cell lines was validated using RT-qPCR. Western blotting was employed for protein expression evaluation. SYT1 overexpression vector was transfected in GBM cells. CCK-8 assay and flow cytometry were performed to detect the malignant phenotypes of GBM cells. There were 901 upregulated and 1086 downregulated DEMs identified, which were prominently enriched in various malignancy-related functions and pathways. Twenty-two hub genes were selected from PPI networks. Survival analysis and experimental validation revealed that four hub genes were tightly associated with GBM prognosis and progression, including SYT1, GRIN2A, KCNA1, and SYNPR. The four genes were significantly downregulated in GBM tissues and cell lines. Overexpressing SYT1 alleviated the proliferation and promoted the apoptosis of GBM cells in vitro. We identify four genes that may be potential molecular markers of GBM, which may provide new ideas for improving early diagnosis and prediction of the disease.
胶质母细胞瘤(GBM)是最常见的原发性颅内恶性肿瘤,患者生存率极低。探索 GBM 的关键分子标志物有助于早期诊断、预后预测和复发监测。本研究旨在通过生物信息学分析和实验验证来探索 GBM 的新型生物标志物。从 GEO 数据库中获取数据集 GSE103229,以搜索差异表达的长链非编码 RNA(DELs)、信使 RNA(DEMs)和 microRNA(DEMis)。选择枢纽基因构建竞争内源性 RNA(ceRNA)网络。利用 GEPIA 数据库对枢纽基因进行生存分析和表达检测。使用 RT-qPCR 验证 GBM 组织样本和细胞系中枢纽基因的表达。使用 Western blot 评估蛋白表达。转染 SYT1 过表达载体于 GBM 细胞中。通过 CCK-8 检测和流式细胞术检测 GBM 细胞的恶性表型。鉴定出 901 个上调和 1086 个下调的 DEMs,这些基因显著富集于多种恶性相关功能和通路。从 PPI 网络中选择 22 个枢纽基因。生存分析和实验验证显示,有四个枢纽基因与 GBM 的预后和进展密切相关,包括 SYT1、GRIN2A、KCNA1 和 SYNPR。这四个基因在 GBM 组织和细胞系中表达显著下调。过表达 SYT1 可减轻体外 GBM 细胞的增殖并促进其凋亡。我们鉴定出四个可能是 GBM 潜在分子标志物的基因,这可能为改善疾病的早期诊断和预测提供新的思路。