Screening and Analysis of Key lncRNA and miRNA Affecting the Occurrence and Proliferation of Human Glioma Cells
Abstract: 脑胶质瘤是一种极度常见颅腔内的原发性恶性肿瘤，患病人群占据所有颅内肿瘤患者的60%。IV级胶质瘤为最高恶性程度，也称为胶质母细胞瘤(胶质母细胞瘤，GBM)，约占全部胶质瘤的55%，且诊断为GBM的患者5年生存率低于6%。许多研究表明，脑胶质瘤中异常表达的lncRNA不仅调控着与癌细胞增殖、凋亡有关的信号转导通路，还与病人的预后有关。利用转录组高通量测序方法，筛选影响脑胶质瘤发生、发展及复发过程中关键通路中的重要基因，对脑胶质瘤的分子诊断、靶向药物的研发及新治疗方案的选择具有重要的价值。本研究通过RNA-seq和生物信息学分析，筛选出在脑胶质瘤组织中差异表达的lncRNA 106种，其中上调表达52种，下调表达54种。microRNA共计15个，其中上调表达8种；下调表达7种。这些差异表达的ncRNA主要参与有机循环化合物代谢过程、胞内运输、细胞蛋白质定位、蛋白质运输、有丝分裂细胞周期、细胞周期调节、DNA代谢过程的正调控、水解酶活性的调节等生物过程、生物调节、应激反应、多细胞有机体过程、细胞成分的组织或生物发生、细胞定位、信号途径、发育过程、生物过程的正调控与负调控。经lncRNA-miRNA-mRNA关联分析，建立了ceRNAs调控网络，明确了lncRNA、miRNA与靶标mRNA之间的对应关系。这些关键lncRNA的筛选，为脑胶质瘤的诊断及治疗提供了新的思路与方向。 Glioma is an extremely common primary malignant tumor in the cranial cavity, which accounts for 60% of all patients with intracranial tumors. Grade IV glioma is the highest degree of malignancy, also called glioblastoma (glioblastoma, GBM), accounting for about 55% of all gliomas, and the 5-year survival rate of patients diagnosed with GBM is lower than 6%. Many studies have shown that the abnormally expressed lncRNA in brain gliomas not only regulates the signal transduction pathways related to cancer cell proliferation and apoptosis, but is also related to the patient’s prognosis. Using transcriptome high-throughput sequencing to screen important genes in key pathways that affect the development, development and recurrence of glioma is of great value for molecular diagnosis of glioma, research and development of targeted drugs and selection of new treatment options. In this study, through RNA-seq and bioinformatics analysis, 106 types of lncRNAs that are differentially expressed in glioma tissues were screened, of which 52 were up-regulated and 54 were down-regulated. There are a total of 15 microRNAs, of which 8 are up-regulated and 7 are down-regulated. These differentially expressed ncRNAs are mainly involved in the metabolic process of organic circulating compounds, intracellular transport, cell protein localization, protein transport, mitotic cell cycle, cell cycle regulation, positive regulation of DNA metabolism, regulation of hydrolase activity and other biological processes and biological regulation, Stress response, multicellular organism process, tissue or biogenesis of cell components, cell location, signal pathway, development process, positive and negative regulation of biological processes. After lncRNA-miRNA-mRNA association analysis, a ceRNAs regulatory network was established, and the correspondence between lncRNA, miRNA and target mRNA was clarified. The screening of these key lncRNAs provides new ideas and directions for the diagnosis and treatment of glioma.
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