Zhang Yulian, Wang Qi, Wang Zai, Zhang Chuanpeng, Xu Xiaoli, Xu Jun, Ren Hongxiang, Shao Xu, Zhen Xueke, Zhang Li, Yu Yanbing
Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, China.
Department of Neurosurgery, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China.
Front Med (Lausanne). 2021 Nov 11;8:739624. doi: 10.3389/fmed.2021.739624. eCollection 2021.
We sought to clarify the clinical relationship between REST/NRSF expression and the prognosis of glioma and explore the REST-associated competitive endogenous RNA (ceRNA) network in glioma. We downloaded RNA-seq, miRNA-seq and correlated clinical data of 670 glioma patients from The Cancer Genome Atlas and analyzed the correlation between REST expression, clinical characteristics and prognosis. Differentially expressed genes (DEGs) were identified with DESeq2 and analyzed with Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) using the Profiler package. Starbase was used to explore the regulatory interaction between REST and miRNAs or LncRNAs. The lncRNA-miRNA-REST ceRNA network was constructed with Cytoscape. RT-qPCR, WB, CCK8, wound-healing, and luciferase assays were performed to validate the ceRNA network. Results showed that REST expression was significantly higher in glioma patients than normal samples. Higher REST expression was significantly associated with worse overall survival, progression-free interval, and worse disease-specific survival in glioma patients. The DEGs of mRNA, miRNA, and lncRNA were identified, and GO and KEGG enrichment analyses were performed. Finally, REST-associated ceRNA networks, including NR2F2-AS1-miR129-REST and HOTAIRM1-miR137-REST, were experimentally validated. Thus, REST may be a prognostic biomarker and therapeutic target in glioma, and its regulatory network validated in this study may provide insights into glioma's molecular regulatory mechanisms.
我们试图阐明REST/NRSF表达与胶质瘤预后之间的临床关系，并探索胶质瘤中与REST相关的竞争性内源性RNA（ceRNA）网络。我们从癌症基因组图谱下载了670例胶质瘤患者的RNA测序、miRNA测序及相关临床数据，并分析了REST表达、临床特征与预后之间的相关性。使用DESeq2鉴定差异表达基因（DEG），并使用Profiler软件包通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）进行分析。利用Starbase探索REST与miRNA或LncRNA之间的调控相互作用。用Cytoscape构建lncRNA-miRNA-REST ceRNA网络。进行RT-qPCR、WB、CCK8、伤口愈合和荧光素酶测定以验证ceRNA网络。结果显示，胶质瘤患者中REST表达明显高于正常样本。在胶质瘤患者中，较高的REST表达与较差的总生存期、无进展生存期及疾病特异性生存期显著相关。鉴定了mRNA、miRNA和lncRNA的DEG，并进行了GO和KEGG富集分析。最后，通过实验验证了包括NR2F2-AS1-miR129-REST和HOTAIRM1-miR137-REST在内的与REST相关的ceRNA网络。因此，REST可能是胶质瘤的一种预后生物标志物和治疗靶点，本研究中验证的其调控网络可能为胶质瘤的分子调控机制提供见解。
