Department of Rheumatology, Children's Hospital of Fudan University, Shanghai, China.
Pediatr Rheumatol Online J. 2023 Jul 28;21(1):75. doi: 10.1186/s12969-023-00855-2.
Juvenile spondyloarthropathies (JSpA) are defined as a heterogeneous group of diseases that start before the age of 16. The study aimed to identify key genes and pathways that are influenced by circRNAs and to screen potential therapeutic agents for JSpA. The study involved the analysis of circRNA expression profiles, identification of circRNA-miRNA-mRNA regulatory networks, and functional annotation of differentially expressed genes. The results of the study may have provided insights into the molecular mechanisms underlying JSpA and potential therapeutic targets for this disease.
In this study, sequencing data of circRNA, miRNA, and mRNA were obtained from the GEO datasets. The data were then analyzed to identify candidates for constructing a circRNA-miRNA-mRNA network based on circRNA-miRNA interactions and miRNA-mRNA interactions. Functional enrichments of genes were performed using the DAVID database. A PPI network was constructed using the STRING database and visualized using Cytoscape software. The MCODE plugin app was used to explore hub genes in the PPI network. The expression changes in immune cells were assessed using the online CIBERSORT algorithm to obtain the proportion of various types of immune cells. Finally, the Connectivity Map L1000 platform was used to identify potential agents for JSpA treatment. Overall, this study aimed to provide a comprehensive understanding of the molecular mechanisms underlying JSpA and to identify potential therapeutic agents for this disease.
A total of 225 differentially expressed circRNAs (DEcircRNAs), 23 differentially expressed miRNAs (DEmiRNAs) and 1324 differentially expressed mRNAs (DEmRNAs) were identified. We integrated 5 overlapped circRNAs, 7 miRNAs and 299 target mRNAs into a circRNA-miRNA-mRNA network. We next identified 10 hub genes based on the PPI network. KEGG pathway analysis revealed that the DEGs were mainly associated with JAK-STAT signal pathway. We found that neutrophils accounted for the majority of all enriched cells. In addition, we discovered several chemicals as potential treatment options for JSpA.
Through this bioinformatics analysis, we suggest a regulatory role for circRNAs in the pathogenesis and treatment of JSpA from the view of a competitive endogenous RNA (ceRNA) network.
青少年脊柱关节病(JSpA)定义为一组在 16 岁之前发病的异质性疾病。本研究旨在确定受 circRNA 影响的关键基因和途径,并筛选 JSpA 的潜在治疗药物。该研究涉及 circRNA 表达谱分析、circRNA-miRNA-mRNA 调控网络的鉴定以及差异表达基因的功能注释。该研究的结果可能为 JSpA 的发病机制和该疾病的潜在治疗靶点提供了新的见解。
在这项研究中,从 GEO 数据集获得了 circRNA、miRNA 和 mRNA 的测序数据。然后对这些数据进行分析,以基于 circRNA-miRNA 相互作用和 miRNA-mRNA 相互作用识别构建 circRNA-miRNA-mRNA 网络的候选物。使用 DAVID 数据库对基因进行功能富集分析。使用 STRING 数据库构建 PPI 网络,并使用 Cytoscape 软件可视化。使用 MCODE 插件程序探索 PPI 网络中的枢纽基因。使用在线 CIBERSORT 算法评估免疫细胞的表达变化,以获得各种类型免疫细胞的比例。最后,使用 Connectivity Map L1000 平台鉴定 JSpA 治疗的潜在药物。总之,本研究旨在全面了解 JSpA 的发病机制,并为该疾病的潜在治疗药物提供依据。
共鉴定出 225 个差异表达的 circRNAs(DEcircRNAs)、23 个差异表达的 miRNAs(DEmiRNAs)和 1324 个差异表达的 mRNAs(DEmRNAs)。我们将 5 个重叠的 circRNAs、7 个 miRNAs 和 299 个靶 mRNAs 整合到一个 circRNA-miRNA-mRNA 网络中。我们根据 PPI 网络确定了 10 个枢纽基因。KEGG 通路分析显示,DEGs 主要与 JAK-STAT 信号通路相关。我们发现中性粒细胞占所有富集细胞的大多数。此外,我们发现了几种可能作为 JSpA 治疗选择的化学物质。
通过这项生物信息学分析,我们从竞争性内源性 RNA(ceRNA)网络的角度提出了 circRNA 在 JSpA 发病机制和治疗中的调节作用。