Zhao Liwen, Zhang Pengfei, Nan Yang, Ren Bingcheng, Ma Haiwen, Xie Jiapeng, Huang Qiang
Department of Neurosurgery, Tianjin Medical University General Hospital Airport Site, Tianjin, China.
Tianjin Medical University, Tianjin, China.
Transl Cancer Res. 2022 May;11(5):1017-1032. doi: 10.21037/tcr-21-2597.
Circular RNA is emerging functional molecule for glioblastoma. However, the function and regulatory of circular RNA (circRNA) remains unclear. In this study, the circRNA sequencing and array data of glioblastoma were analyzed by multiple bioinformatics methods to establish a potential molecular sponge mechanism regulation network.
Gene Expression Omnibus datasets were used to extract circRNAs. CircInteractome was used to predict microRNAs binding to circRNAs. Chinese Glioma Gene Atlas database was used to screen the microRNAs with expression and survival trends. MiRabel database was used to predict potential gene targets of microRNAs. The Cancer Genome Atlas database was used to screen the gene targets of sponge network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were to explain the gene targets functions. R software, Cytoscape software and Bioinformatics website were used to establish the network and visualize the results.
Hsa_circ_0000219, hsa_circ_0001073 and hsa_circ_0070700 were selected from more than 2000 differentially expressed circRNAs of Gene Expression Omnibus Series (GSE) GSE146463, GSE92322 and GSE86202 datasets. Hsa-miR-1248 and hsa-miR-1290 were up regulated and related to glioblastoma poor prognosis. Targets of these microRNAs including ARHGEF7, CELA2b, RNF11, YPEL1 and ZNF37a were also screened via expression and survival data. Gene targets function were mainly enriched in signal transduction, cell plasma membrane, ATP binding and calcium signaling pathway.
A circRNA molecular sponge regulatory network including hsa-miR-1248 and hsa-miR-1290 has been established. In this network, hsa_circ_0001073, hsa_circ_0070700, hsa_circ_0000219, hsa-miR-1248, hsa-miR-1290, and RNF11 may have the potential being emerging glioblastoma therapeutic targets. However, their function and significance for glioblastoma need further experiments to verify.
环状RNA是一种在胶质母细胞瘤中崭露头角的功能性分子。然而，环状RNA（circRNA）的功能和调控机制仍不清楚。在本研究中，通过多种生物信息学方法分析了胶质母细胞瘤的circRNA测序和阵列数据，以建立一个潜在的分子海绵机制调控网络。
利用基因表达综合数据库（Gene Expression Omnibus datasets）提取circRNAs。使用CircInteractome预测与circRNAs结合的微小RNA（microRNAs）。利用中国胶质瘤基因图谱数据库（Chinese Glioma Gene Atlas database）筛选具有表达和生存趋势的微小RNA。使用MiRabel数据库预测微小RNA的潜在基因靶点。利用癌症基因组图谱数据库（The Cancer Genome Atlas database）筛选海绵网络的基因靶点。通过基因本体论（Gene Ontology）和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes）分析来解释基因靶点的功能。使用R软件、Cytoscape软件和生物信息学网站建立网络并可视化结果。
从基因表达综合数据库系列（Gene Expression Omnibus Series，GSE）GSE146463、GSE92322和GSE86202数据集中的2000多个差异表达的circRNAs中筛选出了hsa_circ_0000219、hsa_circ_0001073和hsa_circ_0070700。hsa-miR-1248和hsa-miR-1290上调，且与胶质母细胞瘤的不良预后相关。还通过表达和生存数据筛选了这些微小RNA的靶点，包括ARHGEF7、CELA2b、RNF11、YPEL1和ZNF37a。基因靶点功能主要富集于信号转导、细胞质膜、ATP结合和钙信号通路。
已建立了一个包括hsa-miR-1248和hsa-miR-1290的circRNA分子海绵调控网络。在这个网络中，hsa_circ_0001073、hsa_circ_0070700、hsa_circ_0000219、hsa-miR-1248、hsa-miR-1290和RNF11可能有潜力成为新出现的胶质母细胞瘤治疗靶点。然而，它们对胶质母细胞瘤的功能和意义需要进一步实验来验证。
