心房颤动患者循环环状RNA表达谱的初步研究

Genome-wide analysis of circulating non-coding RNA expression profile in atrial fibrillation patients

目的利用基因芯片筛选心房颤动(房颤)患者外周血单核细胞中差异表达的环状RNAs(circRNAs),初步探讨circRNAs在房颤发生发展中的作用。方法连续入选2019年10月1日至10日在泰州市人民医院拟消融治疗的4例房颤患者和4例正常对照者,应用芯片技术检测外周血单核细胞circRNAs差异表达,进行基因本体论(GO)、代谢信号通路(pathway)分析,建立circRNAs-miRNAs共表达网络。结果初步筛选出120条差异表达circRNAs,上调65条,下调55条。GO分析富集最大的生物过程包含磷脂酰乙醇胺酰基链重塑、磷脂酰胆碱酰基链重塑、磷脂生物合成等,富集最大的细胞组成包含特殊颗粒、细胞表面、细胞外区等,富集最大的分子功能包含2-酰基甘油-3-磷酸酰基转移酶活性、跨膜信号受体活性、1-酰基甘油-3-磷酸酰基转移酶活性等。京都基因与基因组百科全书(KEGG)分析提示差异表达circRNAs相关信号通路主要涉及炎症和免疫系统。circRNA_7571、circRNA_4648、circRNA_4631和circRNA_2875是共表达网络中结合节点最多的前4个circRNAs,hsa-miR-128-3p是共表达网络中与circRNAs作用最多的节点。结论房颤患者外周血单核细胞存在差异表达circRNAs,与房颤的发病机制可能相关。circRNA_7571、circRNA_4648、circRNA_4631和circRNA_2875是共表达网络中结合节点最多的前4个circRNAs。circRNA-hsa-miR-123p在房颤发病机制中可能起关键性作用。

Objective To detect differentially expressed circulating non-coding RNAs(circRNAs)in human monocytes from atrial fibrillation(AF)patients and healthy controls using microarray and explore the role of cicRNAs in the occurrence and development of AF.Methods The peripheral blood monocytes of 4 patients with AF and 4 healthy subjects in Jiangsa Taizhou People’s Hospital,from 1st-10th October 2019,were collected for gene chip technology to detect differentially expressed circRNAs.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)analyses were performed to identify the functions of differentially expressed genes and related pathways.Results There were 120 circRNAs differentially expressed,of which 65 were up-regulated and 55 were down-regulated.GO analysis showed that differentially expressed genes enriched in differentially expressed transcripts in biological process were mainly involved in phosphatidylethanolamine acyl-chain remodeling,phosphatidylcholine acyl-chain remodeling and phospholipid biosynthetic process.Differentially expressed transcripts in cellular component were mainly involved in specific granule lumen,cell surface and extracellular region et al.Differentially expressed transcripts in molecular function were mainly involved in 2-acylglycerol-3-phosphate O-acyltransferase activity,transmembrane signaling receptor activity and 1-acylglycerol-3-phosphate O-acyltransferase activity et al.KEGG enrichment pathway analysis showed that some of the enrichment pathways associated with differentially expressed circRNAs include infectious diseases and immune system,etc.Network analysis uncovered four key circRNAs,which were circRNA_7571,circRNA_4648,circRNA_4631and circRNA_2875.hsa-miR-128-3p was the highest positive correlated miRNA in the networks.Conclusion There were differentially expressed circRNAs in human monocytes from AF patients.circRNAs-hsa-miR-128-3p-mediated network may play a critical role in the pathogenesis of AF.