[关键词]
[摘要]
环状RNA(circRNAs)是一种内源性非编码RNA,与生长发育过程以及神经系统退行性病变、肿瘤以及动脉粥样硬化(AS)等疾病密切相关。然而,circRNAs在AS中的作用尚不清楚。本研究可能为诊断和治疗AS提供候选靶点及理论依据。我们通过分析从基因表达综合数据库(GEO)鉴定出的DECs在外泌体中的表达水平,选择hsa_circ_0003645进行后续分析。之后,我们通过CSCD在线数据库鉴定出hsa_circ_0003645具有较高的蛋白质编码能力,含有eIF4AIII和TDP-43两个结合位点,可能与56个miRNA发生相互作用,并对靶基因进行预测分析和富集分析。接着通过构建PPI网络筛选出排名前20的关键基因并进行GO和KEGG富集分析,结果发现hsa_circ_0003645的20个关键基因的主要富集在protein ubiquitination、regulation of cell motility、cell periphery、FoxO signaling pathway、Focal adhesion、Wnt signaling pathway。最后通过Enrichr数据库的DrugMatrix分析与20种与关键基因相互作用的小分子药物,这些结果说明这些小分子药物可能具有治疗AS的潜在能力。综上所述,本研究所鉴定的hsa_circ_0003645、eIF4AIII和关键基因有助于我们了解AS的发病机制和进展,也可能有助于为AS的诊断和治疗提供候选靶点。
[Key word]
[Abstract]
Circular RNAs (circRNAs) is an endogenous non-coding RNA, which is closely related to the growth and development process, neurodegenerative diseases, tumors and atherosclerotic (AS). However, the role of circRNAs in AS remain unclear This study may provide candidate targets and theoretical basis for diagnosis and treatment of AS. We analyzed the expression level of DEGs in exosomes indentified from the Gene Expression Comprehensive Database (GEO), and selected hsa_circ_0003645 for subsequent analysis by analyzing the expression level of DECs in exosomes. Afterwards, we identified through the CSCD online database that hsa_circ_0003645 has high protein coding ability, contains two binding sites of eIF4AIII and TDP-43, which may interact with 56 miRNAs, and perform predictive analysis and enrichment analysis on target genes. Next, the top 20 key genes were screened out by constructing a PPI network and analyzed by GO and KEGG enrichment. The results showed that the 20 key genes of hsa_circ_0003645 were mainly enriched in protein ubiquitination, regulation of cell motility, cell periphery, FoxO signaling pathway, Focal adhesion, Wnt signaling pathway. Finally, the DrugMatrix of the Enrichr database was used to analyze 20 small molecule drugs that interact with key genes. These results indicate that these small molecule drugs may have the potential to treat AS. To sum up, the hsa_circ_0003645, eIF4AIII, and hub genes identified in this study are helpful for us to understand the pathogenesis and progress of AS, and may also help to provide candidate targets for the diagnosis and treatment of AS.
[中图分类号]
[基金项目]
内蒙古自治区高等学校科学研究项目 NJZY18103 内蒙古自治区自然科学基金项目 2018MS08015 内蒙古医科大学附属医院博士启动金项目 NYFYBS 2018