Abstract：
Coronary heart disease (CHD) is a prevalent global cause of death. Research suggests that circular RNAs (circRNAs) play a role in the development of CHD. In this study, we investigated the expression of hsa_circRNA_0000284 in peripheral blood leukocytes (PBLs) obtained from a cohort of 94 CHD patients aged over 50 years, as well as 126 age-matched healthy controls (HC). An in vitro inflammatory and oxidative injury cell model that simulates CHD was used to evaluate changes in hsa_ circRNA _0000284 under stress. CRISPR/Cas9 technology was used to evaluate changes in hsa_circRNA_0000284 expression. An hsa_ circRNA_0000284 overexpression and silencing cell model was used to analyze the biological functions of hsa_circRNA_0000284. Bioinformatics, qRT-PCR, viral transfection technology, and luciferase assays were used to evaluate the potential hsa_circRNA_0000284/miRNA-338-3p/ETS1 axis. Western blotting analysis was performed to detect protein expression. Herein, PBLs from CHD patients exhibited downregulation of hsa_circRNA_0000284 expression. Exposure to oxidative stress and inflammation can induce damage to human umbilical endothelial cells, resulting in the downregulation of hsa_circRNA_0000284 expression. The expression of hsa_circRNA_0000284 in EA-hy926 cells was significantly reduced after the AluSq2 element of hsa_circRNA_0000284 had been knocked out. The expression of hsa_circRNA_0000284 affected proliferation, cycle distribution, aging, and apoptosis in EA-hy926 cells. Consistent with the results of cell transfection experiments and luciferase assays, Western blotting showed that hsa_circRNA_0000284 plays a role in the regulation of hsa-miRNA-338-3p expression. Subsequently, hsa-miRNA-338-3p was found to be involved in the regulation of ETS1 expression.Communicated by Ramaswamy H. Sarma.
摘要：
冠心病（CHD）是全球普遍的死亡原因。研究表明环状RNA（circularRNAs，circRNAs）在CHD的发展中起作用。在这项研究中,我们研究了hsa_circRNA_0000284在外周血白细胞（PBLs）中的表达，这些白细胞来自94名年龄超过50岁的冠心病患者，以及126个年龄匹配的健康对照（HC）。模拟CHD的体外炎症和氧化损伤细胞模型用于评估应激下hsa_circRNA_0000284的变化。CRISPR/Cas9技术用于评估hsa_circRNA_0000284表达的变化。使用hsa_circRNA_0000284过表达和沉默细胞模型来分析hsa_circRNA_0000284的生物学功能。生物信息学,qRT-PCR,病毒转染技术,和荧光素酶测定用于评估潜在的hsa_circRNA_0000284/miRNA-338-3p/ETS1轴。进行蛋白质印迹分析以检测蛋白质表达。在这里，来自CHD患者的PBL表现出hsa_circircRNA_0000284表达的下调。暴露于氧化应激和炎症可以诱导人脐内皮细胞的损伤，导致hsa_circRNA_0000284表达下调。敲除hsa_circRNA_0000284的AluSq2元件后，EA-hy926细胞中hsa_circRNA_0000284的表达显着降低。hsa_circRNA_0000284的表达影响增殖，周期分布,老化，EA-hy926细胞凋亡。与细胞转染实验和荧光素酶测定的结果一致，Western印迹显示hsa_circRNA_0000284在调控hsa-miRNA-338-3p表达中起作用。随后，发现hsa-miRNA-338-3p参与ETS1表达的调节。由RamaswamyH.Sarma沟通。
