Department of Histology and Embryology, School of Pre-clinical Medicine, Guangxi Medical University, Nanning, 530021, China.
Department of Neurology, the First Affiliated Hospital, Guangxi Medical University, Nanning, 530021, China.
Curr Med Sci. 2022 Jun;42(3):584-596. doi: 10.1007/s11596-022-2593-5. Epub 2022 Jun 8.
Glioblastoma (GBM) is the most common, invasive, and malignant primary brain tumor with a poor prognosis and high recurrence rate. It's known that some microRNAs (miRNAs) which are associated with tumorigenesis and progression can be considered as prognostic and therapeutic targets in tumors including GBM. This study aims to highlight the potential role of the core miRNAs in GBM and their potential use as a prognostic and therapeutic biomarker.
Differentially expressed miRNAs (DEmiRNAs) were identified in GBM by integrating miRNA-sequencing results and a GBM microarray dataset from the Gene Expression Omnibus (GEO) database through bioinformatics tools. The dysregulated miRNAs were identified by survival analysis through Chinese Glioma Genome Atlas (CGGA). Target genes of the dysregulated miRNAs were predicted on MiRWalk and miRTarBase database. TAM2.0 database, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were used to analyze the function of the dysregulated miRNAs. Subsequently, protein-protein interaction (PPI) network analysis was used to identify the top 20 hub targets of the up-regulated and down-regulated miRNAs, respectively. Then, core miRNAs in GBM were identified by constructing dysregulated miRNA-differentially expressed hub gene networks. Validation of the core miRNAs expression was detected in 41 GBM tissues compared to 8 normal brain tissues. Furthermore, the potential biomarkers were identified by clinical correlation analysis and survival analysis.
Totally, 68 intersecting DEmiRNAs were identified, 40 of which were upregulated and the other 28 miRNAs were downregulated. Two upregulated and 4 downregulated miRNAs showed prognostic significance. Most differentially expressed hub genes were regulated by the miR-28-5p and miR-1224-5p, which were respectively upregulated and downregulated in GBM. The correlation between miR-1224-5p level and recurrence was statistically significant (P=0.011). Survival analysis showed that high miR-28-5p level and high miR-1224-5p level were both associated with better prognosis. Moreover, high miR-1224-5p level was an independent prognosis factor for GBM patients according to the cox regression analysis.
MiRNA-1224-5p could be a potential target for the prognosis and treatment in GBM.
胶质母细胞瘤（GBM）是最常见、侵袭性最强和恶性程度最高的原发性脑肿瘤，预后不良，复发率高。已知一些与肿瘤发生和进展相关的 microRNAs（miRNAs）可以被认为是包括 GBM 在内的肿瘤的预后和治疗靶点。本研究旨在强调核心 miRNAs 在 GBM 中的潜在作用及其作为预后和治疗生物标志物的潜在用途。
通过整合 miRNA 测序结果和基因表达综合数据库（GEO）数据库中的 GBM 微阵列数据集，使用生物信息学工具鉴定 GBM 中的差异表达 miRNAs（DEmiRNAs）。通过中国脑胶质瘤基因组图谱（CGGA）中的生存分析鉴定失调 miRNAs。使用 TAM2.0 数据库、基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析来分析失调 miRNAs 的功能。随后，使用蛋白质-蛋白质相互作用（PPI）网络分析分别鉴定上调和下调 miRNAs 的前 20 个核心靶标。然后，通过构建失调 miRNA-差异表达核心基因网络来鉴定 GBM 中的核心 miRNAs。与 8 例正常脑组织相比，检测了 41 例 GBM 组织中核心 miRNAs 的表达验证。此外，通过临床相关性分析和生存分析鉴定潜在的生物标志物。
总共鉴定出 68 个相交的 DEmiRNAs，其中 40 个上调，另外 28 个下调。两个上调和四个下调的 miRNAs 显示出预后意义。大多数差异表达的核心基因受 miR-28-5p 和 miR-1224-5p 的调节，miR-28-5p 和 miR-1224-5p 在 GBM 中分别上调和下调。miR-1224-5p 水平与复发之间的相关性具有统计学意义（P=0.011）。生存分析表明，高 miR-28-5p 水平和高 miR-1224-5p 水平均与更好的预后相关。此外，根据 Cox 回归分析，高 miR-1224-5p 水平是 GBM 患者的独立预后因素。
miR-1224-5p 可能是 GBM 预后和治疗的潜在靶点。
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