Rong Zheyi, Yan Jingyi, Wei Junbo
Department of Cardiovascular Medicine, Renhe Hospital of Baoshan District, Shanghai, China.
General Practice, Community Health Center of Luoging, Shanghai, China.
Minerva Cardiol Angiol. 2025 Jun 27. doi: 10.23736/S2724-5683.25.06657-8.
Circular RNAs (circRNAs) are implicated in the pathogenesis of acute myocardial infarction (AMI). Current research aims to evaluate the diagnostic and functional value of circFOXP1 in AMI patients.
The expression of circFOXP1 was assessed using RT-qPCR, and its diagnostic potential was determined through receiver operating characteristic (ROC) curve. The target gene of circFOXP1 was identified using a luciferase reporter assay. An in vitro hypoxia/reoxygenation (H/R) model was established in AC16 cells, while an AMI model was constructed in C57BL/6 mice. The proliferation and apoptosis of AC16 cells were evaluated using CCK8 and flow cytometry (FCM). The impact of circFOXP1 on inflammation was measured by assessing levels of TNF-α, IL-1β, and IL-6, while the effects of circFOXP1 on oxidative stress were evaluated through measurements of reactive oxygen species (ROS), glutathione (GSH), and lactate dehydrogenase (LDH) levels.
circFOXP1 expression was found to be downregulated in AMI patients compared to controls. The ROC curve indicated an area under the curve (AUC) was 0.881 (95%CI=0.847-0.915), with a sensitivity of 0.930 and a specificity of 0.785. Additionally, miR-9-3p was identified as a direct target gene of circFOXP1. High levels of circFOXP1 did not significantly affect f the proliferation of H/R stimulated AC16 cells; however, increased circFOXP1 resulted in significant reduction in cell apoptosis (P<0.001). TNF-α, IL-1β, and IL-6 levels were significantly lower in pcDNA3.1-circFOXP1-transfected cells (P<0.001). ROS concentration and LDH level were markedly reduced in these cells (P<0.01), while GSH level (P<0.001) was significantly elevated. miR-9-3p, as a direct target gene of circFOXP1, was found to reverse the effects of circFOXP1 on H/R AC16 cells and AMI model.
circFOXP1 was decreased in AMI patients and may serve as a diagnostic marker for AMI. Overexpression of circFOXP1 was shown to suppress apoptosis, inflammation, and oxidative stress via miR-9-3p in AC16 cells and the AMI model.
环状RNA（circRNAs）与急性心肌梗死（AMI）的发病机制有关。当前研究旨在评估circFOXP1在AMI患者中的诊断和功能价值。
采用逆转录定量聚合酶链反应（RT-qPCR）评估circFOXP1的表达，并通过受试者工作特征（ROC）曲线确定其诊断潜力。使用荧光素酶报告基因检测法鉴定circFOXP1的靶基因。在AC16细胞中建立体外缺氧/复氧（H/R）模型，在C57BL/6小鼠中构建AMI模型。使用细胞计数试剂盒-8（CCK8）和流式细胞术（FCM）评估AC16细胞的增殖和凋亡。通过评估肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）水平来测量circFOXP1对炎症的影响，通过测量活性氧（ROS）、谷胱甘肽（GSH）和乳酸脱氢酶（LDH）水平来评估circFOXP1对氧化应激的影响。
与对照组相比，发现AMI患者中circFOXP1表达下调。ROC曲线显示曲线下面积（AUC）为0.881（95%置信区间=0.847-0.915），灵敏度为0.930，特异性为0.785。此外，miR-9-3p被鉴定为circFOXP1的直接靶基因。高水平的circFOXP1对H/R刺激的AC16细胞的增殖没有显著影响；然而，circFOXP1的增加导致细胞凋亡显著减少（P<0.001）。在转染了pcDNA3.1-circFOXP1的细胞中，TNF-α、IL-1β和IL-6水平显著降低（P<0.001）。这些细胞中的ROS浓度和LDH水平显著降低（P<0.01），而GSH水平（P<0.001）显著升高。发现作为circFOXP1直接靶基因的miR-9-3p可逆转circFOXP1对H/R AC16细胞和AMI模型的影响。
AMI患者中circFOXP1降低，可能作为AMI的诊断标志物。在AC16细胞和AMI模型中，circFOXP1的过表达通过miR-9-3p抑制细胞凋亡、炎症和氧化应激。
