Gu Yan, Ma Xiao, Li Jing, Ma Yuhong, Zhang Yun
Affiliated Hospital of Inner Mongolia Medical University Hohhot 010050, The Inner Mongolia Autonomous Region, P. R. China.
Chinese People's Liberation Army No. 969 Hospital Hohhot 010051, The Inner Mongolia Autonomous Region, P. R. China.
Am J Transl Res. 2021 May 15;13(5):4137-4151. eCollection 2021.
Atherosclerosis, a chronic inflammatory disease, is the primary cause of most cardiovascular diseases. Circular RNAs (circRNAs) were reported to serve as post-transcriptional regulators and diagnostic markers in various diseases, but the underlying correlation between circRNAs and atherosclerosis remains elusive. In this study, we downloaded the microarray dataset GSE107522 from the Gene Expression Omnibus (GEO) and identified nine differentially expressed circRNAs (DECs). DECs expression in exosomes were investigated, and hsa_circ_0005699 was selected for subsequent analysis. We then identified 14 RNA-binding proteins (RBPs) and 71 possible hsa_circ_0005699-interacting microRNAs. Subsequently, target gene prediction and enrichment analyses were performed. The enriched pathways of RBP eIF4AIII include spliceosome, cell cycle, and pathways in cancer. We constructed a protein-protein interaction network, and 20 hub genes were identified using Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape. Hub gene analysis revealed significant enrichment in mRNA splicing via the spliceosome, RNA splicing, protein binding, neurotrophin signaling pathway, and Ras signaling pathway. Using DrugMatrix of the Enrichr database, we identified 16 most significant small-molecule compounds that interacted with hub genes. Finally, seven hub genes (NEDD4L, FBXO44, FBXO27, WSB1, FBXW8, UBE2F, and ASB1) in cluster 1 were considered key targets associated with atherosclerosis according to MCODE analysis and the intersection between the module and hub genes. Thus, hsa_circ_0005699, RBP eIF4AIII, and the seven identified hub genes (NEDD4L, FBXO44, FBXO27, WSB1, FBXW8, UBE2F, and ASB1) could help to elucidate the pathogenesis and progression of atherosclerosis. This work may contribute to providing candidate targets for the diagnosis and treatment of atherosclerosis.
动脉粥样硬化是一种慢性炎症性疾病，是大多数心血管疾病的主要病因。据报道，环状RNA（circRNA）在多种疾病中作为转录后调节因子和诊断标志物，但circRNA与动脉粥样硬化之间的潜在关联仍不清楚。在本研究中，我们从基因表达综合数据库（GEO）下载了微阵列数据集GSE107522，并鉴定出9种差异表达的环状RNA（DECs）。研究了外泌体中DECs的表达，并选择hsa_circ_0005699进行后续分析。然后，我们鉴定出14种RNA结合蛋白（RBP）和71种可能与hsa_circ_0005699相互作用的微小RNA。随后，进行了靶基因预测和富集分析。RBP eIF4AIII的富集途径包括剪接体、细胞周期和癌症相关途径。我们构建了一个蛋白质-蛋白质相互作用网络，并使用检索相互作用基因/蛋白质的搜索工具和Cytoscape软件鉴定出20个枢纽基因。枢纽基因分析显示，在通过剪接体进行的mRNA剪接、RNA剪接、蛋白质结合、神经营养因子信号通路和Ras信号通路中存在显著富集。使用Enrichr数据库的DrugMatrix，我们鉴定出16种与枢纽基因相互作用的最显著小分子化合物。最后，根据MCODE分析以及模块与枢纽基因之间的交集，第1簇中的7个枢纽基因（NEDD4L、FBXO44、FBXO27、WSB1、FBXW8、UBE2F和ASB1）被认为是与动脉粥样硬化相关的关键靶点。因此，hsa_circ_0005699、RBP eIF4AIII以及鉴定出的7个枢纽基因（NEDD4L、FBXO44、FBXO27、WSB1、FBXW8、UBE2F和ASB1）可能有助于阐明动脉粥样硬化的发病机制和进展。这项工作可能有助于为动脉粥样硬化的诊断和治疗提供候选靶点。
