Identification of a circRNA-miRNA-mRNA network to explore the effects of circRNAs on pathogenesis and treatment of spinal cord injury
Identification of a circRNA-miRNA-mRNA network to explore the effects of circRNAs on pathogenesis and treatment of spinal cord injury
复制标题
鉴定circRNA-miRNA-mRNA网络，探讨circRNA对脊髓损伤发病机制和治疗的影响
DOI：
10.1016/j.lfs.2020.118039
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发表时间：
2020-09-15
期刊：
影响因子：
6.1
通讯作者：
Feng, Shiqing
中科院分区：
文献类型：
--
作者：
Peng, Peng;Zhang, Bin;Feng, Shiqing
目的：许多研究表明circRNA与人类疾病密切相关。尽管如此，circRNA 影响脊髓损伤 (SCI) 的潜在机制尚不完全清楚。本研究的目的是探讨circRNA在SCI中的调控作用。主要方法：从基因表达综合(GEO)数据集中获得circRNA、miRNA和mRNA的测序数据。候选者被确定构建基于 circRNA-miRNA 相互作用和 miRNA-mRNA 相互作用的 circRNA-miRNA-mRNA 网络。进行蛋白质-蛋白质相互作用 (PPI) 分析以确定枢纽基因，并应用连接图 (CMap) 分析确定 SCI 的潜在治疗靶点。 主要发现：总共鉴定了 1656 个差异表达的 circRNA (DEcircRNA)、71 个差异表达的 miRNA (DEmiRNA) 和 2782 个差异表达的 mRNA (DEmRNA)。我们将 4 个重叠的 circRNA、6 个 miRNA 和 101 个目标 mRNA 整合到一个 circRNA-miRNA-mRNA 网络中。接下来，我们基于 PPI 网络确定了两个 hub 基因（DDIT4、EZR），并确定了 5 个 circRNA-miRNA-hub 基因调控轴。此外，我们还发现了三种化学物质（坦斯匹霉素、氟维司群、卡马西平）作为 SCI 的潜在治疗选择。 意义：我们的研究从竞争性内源性 RNA (ceRNA) 网络的角度表明，circRNA 在 SCI 的发病机制和治疗中具有调节作用。
Aims: Many studies have demonstrated that circRNAs are closely associated with human diseases. Nonetheless, the potential mechanism by which circRNAs impacts spinal cord injury (SCI) is not fully understood. The aim of this study was to explore the regulatory roles of circRNAs in SCI.Main methods: The sequencing data of circRNA, miRNA and mRNA were obtained from Gene Expression Omnibus (GEO) datasets. Candidates were identified to construct a circRNA-miRNA-mRNA network based on circRNA-miRNA interactions and miRNA-mRNA interactions. Protein-protein interactions (PPI) analysis was performed to determine hub genes, and a connectivity map (CMap) analysis was applied to determine potential therapeutic targets for SCI.Key findings: A total of 1656 differentially expressed circRNAs (DEcircRNAs), 71 differentially expressed miRNAs (DEmiRNAs) and 2782 differentially expressed mRNAs (DEmRNAs) were identified. We integrated four overlapped circRNAs, six miRNAs and 101 target mRNAs into a circRNA-miRNA-mRNA network. We next identified two hub genes (DDIT4, EZR) based on the PPI network and identified five circRNA-miRNA-hub gene regulatory axes. In addition, we discovered three chemicals (tanespimycin, fulvestrant, carbamazepine) as potential treatment options for SCI.Significance: Our study suggests a regulatory role for circRNAs in the pathogenesis and treatment of SCI from the view of a competitive endogenous RNA (ceRNA) network.