Department of Neurology, Peking University Shenzhen Hospital, Shenzhen, 518036, China.
Department of Neurosurgery, Peking University Shenzhen Hospital, Shenzhen, 518036, China.
BMC Med Genomics. 2024 Apr 9;17(1):83. doi: 10.1186/s12920-024-01851-5.
Glioblastoma multiforme (GBM) is the most common primary CNS tumor, characterized by high mortality and heterogeneity. However, the related lncRNA signatures and their target microRNA (miRNA) for GBM are still mostly unknown. Therefore, it is critical that we discover lncRNA markers in GBM and their biological activities.
GBM-related RNA-seq data were obtained from the Cancer Genome Atlas (TCGA) database. The "edger" R package was used for differently expressed lncRNAs (DELs) identification. Then, we forecasted prospective miRNAs that might bind to lncRNAs by Cytoscape software. Survival analysis of those miRNAs was examined by the starBase database, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the miRNAs' target genes was conducted by the Gene Set Enrichment Analysis (GSEA) database and R software. Moreover, the proliferative ability of unc-5 netrin receptor B antisense RNA 1 (UNC5B-AS1) cells was evaluated by Cell Counting Kit-8 (CCK-8) analysis. Mechanistically, the regulatory interaction between UNC5B-AS1 and miRNA in GBM biological processes was studied using CCK-8 analysis.
Our results indicated that overexpression of UNC5B-AS1 has been shown to suppress GBM cell growth. Mechanistically, miR-24-3p in GBM was able to alleviate the anti-oncogenic effects of UNC5B-AS1 on cell proliferation.
The discovery of the novel UNC5B-AS1-miR-24-3p network suggests possible lncRNA and miRNA roles in the development of GBM, which may have significant ramifications for the analysis of clinical prognosis and the development of GBM medications.
多形性胶质母细胞瘤（GBM）是最常见的原发性中枢神经系统肿瘤，具有高死亡率和异质性的特点。然而，GBM 相关的长链非编码 RNA（lncRNA）特征及其靶微小 RNA（miRNA）仍大多未知。因此，发现 GBM 中的 lncRNA 标志物及其生物学活性至关重要。
从癌症基因组图谱（TCGA）数据库中获取 GBM 相关的 RNA-seq 数据。使用“edger”R 包识别差异表达的 lncRNAs（DELs）。然后，我们通过 Cytoscape 软件预测可能与 lncRNA 结合的潜在 miRNA。通过 starBase 数据库对这些 miRNA 的生存分析进行了检验，通过 Gene Set Enrichment Analysis（GSEA）数据库和 R 软件对 miRNA 靶基因的京都基因与基因组百科全书（KEGG）富集分析进行了检验。此外，通过细胞计数试剂盒-8（CCK-8）分析评估了 unc-5 神经导向因子 B 反义 RNA 1（UNC5B-AS1）细胞的增殖能力。从机制上，通过 CCK-8 分析研究了 GBM 生物学过程中 UNC5B-AS1 与 miRNA 之间的调控相互作用。
我们的结果表明，UNC5B-AS1 的过表达已被证明可抑制 GBM 细胞生长。从机制上讲，miR-24-3p 能够减轻 UNC5B-AS1 对细胞增殖的抑癌作用。
新型 UNC5B-AS1-miR-24-3p 网络的发现提示 lncRNA 和 miRNA 可能在 GBM 的发展中发挥作用，这可能对临床预后分析和 GBM 药物的开发具有重要意义。
