Department of Cardiology, The Second People's Hospital of Hefei (Hefei Hospital Affiliated to Medical University of Anhui).
Int Heart J. 2023 Nov 30;64(6):1113-1124. doi: 10.1536/ihj.22-452. Epub 2023 Nov 14.
Acute myocardial infarction (AMI) is a common coronary artery disease. This study attempted to reveal the impact of circ-SUZ12 (hsa_circ_0042961) on cardiomyocyte injury after exposure to hypoxia.Circ-SUZ12 was screened out from the GEO dataset GSE169594. RNA expression and protein level were detected by quantitative real-time PCR (qRT-PCR) and Western blot, respectively. The characteristics of circ-SUZ12 were identified by measuring its resistance to Rnase R or actinomycin D (Act D) treatment. CCK-8 and EdU assays were performed to explore the viability of AC16 cells. Cell apoptosis was assessed through TUNEL assay and flow cytometry analysis. Mechanism experiments were performed to investigate the downstream molecular mechanism of circ-SUZ12.Circ-SUZ12 was highly expressed in blood samples of AMI patients in the GEO dataset and lowly expressed in hypoxia-treated cardiomyocytes. Overexpression of circ-SUZ12 reversed hypoxia-induced cardiomyocyte injury. Circ-SUZ12 regulated SUZ12 polycomb repressive complex 2 subunit (SUZ12) expression by recruiting FUS protein. SUZ12 activated the Wnt/β-catenin signaling pathway by increasing the H3K27me3 level in microRNA (miR)-526b-5p promoter to release catenin beta 1 (CTNNB1). CTNNB1 depletion reversed the effect of circ-SUZ12 on the viability and apoptosis of hypoxia-induced cardiomyocytes.Circ-SUZ12 protects cardiomyocytes from hypoxia-induced dysfunction through upregulating SUZ12 expression to activate the Wnt/β-catenin signaling pathway.
急性心肌梗死（AMI）是一种常见的冠状动脉疾病。本研究试图揭示circ-SUZ12（hsa_circ_0042961）在缺氧暴露后对心肌细胞损伤的影响。circ-SUZ12 是从 GEO 数据集 GSE169594 中筛选出来的。通过定量实时 PCR（qRT-PCR）和 Western blot 分别检测 RNA 表达和蛋白水平。通过测量其对核糖核酸酶 R 或放线菌素 D（Act D）处理的抗性来鉴定 circ-SUZ12 的特征。通过 CCK-8 和 EdU 测定法研究 AC16 细胞的活力。通过 TUNEL 测定法和流式细胞术分析评估细胞凋亡。通过机制实验研究 circ-SUZ12 的下游分子机制。在 GEO 数据集和低表达在缺氧处理的心肌细胞中的 AMI 患者的血液样本中高度表达。circ-SUZ12 的过表达逆转了缺氧诱导的心肌细胞损伤。circ-SUZ12 通过募集 FUS 蛋白来调节 SUZ12 多梳抑制复合物 2 亚基（SUZ12）的表达。SUZ12 通过增加 miR-526b-5p 启动子中的 H3K27me3 水平来激活 Wnt/β-catenin 信号通路，从而释放连环蛋白β 1（CTNNB1）。CTNNB1 耗竭逆转了 circ-SUZ12 对缺氧诱导的心肌细胞活力和凋亡的影响。circ-SUZ12 通过上调 SUZ12 表达来激活 Wnt/β-catenin 信号通路，从而保护心肌细胞免受缺氧引起的功能障碍。
