Wei Bo, Wang Le, Zhao Jingwei
Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Department of Ophthalmology, The First Hospital of Jilin University, Jilin University, Changchun, Jilin 130021, P.R. China.
Oncol Lett. 2021 Jan;21(1):58. doi: 10.3892/ol.2020.12320. Epub 2020 Nov 19.
Glioma is the most common type of brain tumor and is associated with a high mortality rate. Despite recent advances in treatment options, the overall prognosis in patients with glioma remains poor. Studies have suggested that circular (circ)RNAs serve important roles in the development and progression of glioma and may have potential as therapeutic targets. However, the expression profiles of circRNAs and their functions in glioma have rarely been studied. The present study aimed to screen differentially expressed circRNAs (DECs) between glioma and normal brain tissues using sequencing data collected from the Gene Expression Omnibus database (GSE86202 and GSE92322 datasets) and explain their mechanisms based on the competing endogenous (ce)RNA regulatory hypothesis. In total, 424 commonly downregulated DECs (with the Gene_symbol annotated in the circBase database) in these two datasets were identified. Using the CircInteractome and Starbase databases, 18 micro (mi)RNAs (miRs) were predicted to interact with DECs, while 22 glioma-related genes obtained from the Comparative Toxicogenomics Database were predicted to be regulated by 15 miRNAs via the miRwalk 2.0 database. A ceRNA network was established based on 115 DECs, 15 miRNAs and 22 mRNAs. LinkedOmics online analysis using The Cancer Genome Atlas (TCGA) data showed that hsa-miR-142-3p/hsa-miR-590-5p and their target gene adenomatous polyposis coli protein (APC) were all significantly associated with overall survival rate and their prognosis trend was opposite, revealing that high expression levels of hsa-miR-142-3p/hsa-miR-590-5 were associated with a poor overall survival rate, while high APC expression with a good overall survival rate. UALCAN analysis using TCGA data of glioblastoma multiforme and the GSE25632 and GSE103229 microarray datasets showed that hsa-miR-142-3p/hsa-miR-590-5p was upregulated and APC was downregulated. Thus, hsa-miR-142-3p/hsa-miR-590-5p-APC-related circ/ceRNA axes may be important in glioma, and hsa_circ_0005114 interacted with both of these miRNAs. Functional analysis showed that hsa_circ_0005114 was involved in insulin secretion, while APC was associated with the Wnt signaling pathway. In conclusion, hsa_circ_0005114-miR-142-3p/miR-590-5p-APC ceRNA axes may be potential targets for the treatment of glioma.
胶质瘤是最常见的脑肿瘤类型，且死亡率很高。尽管近年来治疗方案有所进展，但胶质瘤患者的总体预后仍然很差。研究表明，环状（circ）RNA在胶质瘤的发生和发展中起重要作用，可能具有作为治疗靶点的潜力。然而，circRNA在胶质瘤中的表达谱及其功能鲜有研究。本研究旨在利用从基因表达综合数据库（GSE86202和GSE92322数据集）收集的测序数据，筛选胶质瘤与正常脑组织之间差异表达的circRNA（DECs），并基于竞争性内源（ce）RNA调控假说解释其机制。在这两个数据集中，共鉴定出424个共同下调的DECs（其基因符号在circBase数据库中有注释）。利用CircInteractome和Starbase数据库，预测有18个微小（mi）RNA（miRs）与DECs相互作用，而通过miRwalk 2.0数据库预测，从比较毒理基因组学数据库获得的22个胶质瘤相关基因受15个miRNA调控。基于115个DECs、15个miRNA和22个mRNA建立了ceRNA网络。使用癌症基因组图谱（TCGA）数据进行的LinkedOmics在线分析表明，hsa-miR-142-3p/hsa-miR-590-5p及其靶基因腺瘤性息肉病 coli 蛋白（APC）均与总生存率显著相关，且它们的预后趋势相反，这表明hsa-miR-142-3p/hsa-miR-590-5高表达与总生存率差相关，而APC高表达与总生存率好相关。使用多形性胶质母细胞瘤的TCGA数据以及GSE25632和GSE103229微阵列数据集进行的UALCAN分析表明，hsa-miR-142-3p/hsa-miR-590-5p上调，APC下调。因此，hsa-miR-142-3p/hsa-miR-590-5p-APC相关的circ/ceRNA轴可能在胶质瘤中起重要作用，且hsa_circ_0005114与这两种miRNA均相互作用。功能分析表明，hsa_circ_0005114参与胰岛素分泌，而APC与Wnt信号通路相关。总之，hsa_circ_0005114-miR-142-3p/miR-590-5p-APC ceRNA轴可能是治疗胶质瘤的潜在靶点。
