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环状RNA Larp4b/微小RNA-298-5p/肌细胞增强因子2C调控血管紧张素II诱导的心肌肥大

CircRNA Larp4b/miR-298-5p/Mef2c Regulates Cardiac Hypertrophy Induced by Angiotensin II.

作者信息

Xie Qihai, Xu Xiangdong, Xiong Danqun, Yao Man, Zhou Yafeng

机构信息

Department of Cardiology, the First Affiliated Hospital of Soochow University, Suzhou, China.

Department of Cardiology, Baoshan Branch, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

出版信息

Int J Sports Med. 2024 Jan;45(1):33-40. doi: 10.1055/a-2172-8171. Epub 2023 Nov 13.

Abstract

Cardiac hypertrophy (CH) is an early marker in the clinical course of heart failure. Circular RNAs (circRNAs) play important roles in human disease. However, the role of circ_Larp4b in myocardial hypertrophy has not been studied. Angiotensin II (Ang II) treated HL-1 cells to induce a CH cell model. Quantitative real-time polymerase chain reaction was used to detect the expression of circ_Larp4b, microRNA-298-5p, and myocyte enhancer factor 2 (Mef2c). Western blot detected the protein level of alpha-actinin-2 (ACTN2), beta-myosin heavy chain (β-MHC), atrial natriuretic peptide (ANP), and Mef2c. The relationship between miR-298-5p and circ_Larp4b or Mef2c was verified by dual-luciferase reporter assay and RNA pull-down assay. Circ_Larp4b and Mef2c were upregulated in HL-1 cells treated with Ang II. Moreover, circ_Larp4b down-regulation regulated the progress of CH induced by Ang II. MiR-298-5p was a target of circ_Larp4b, and Mef2c was a target of miR-298-5p. Overexpressed Mef2c reversed the cell size inhibited by miR-298-5p in Ang II-induced HL-1 cells. Circ_Larp4b regulated CH progress by regulating miR-298-5p/Mef2c axis.

摘要

心肌肥厚(CH)是心力衰竭临床病程中的一个早期标志物。环状RNA(circRNA)在人类疾病中发挥着重要作用。然而,circ_Larp4b在心肌肥厚中的作用尚未得到研究。用血管紧张素II(Ang II)处理HL-1细胞以诱导CH细胞模型。采用定量实时聚合酶链反应检测circ_Larp4b、微小RNA-298-5p和肌细胞增强因子2(Mef2c)的表达。蛋白质印迹法检测α-辅肌动蛋白-2(ACTN2)、β-肌球蛋白重链(β-MHC)、心钠素(ANP)和Mef2c的蛋白水平。通过双荧光素酶报告基因检测和RNA下拉实验验证miR-298-5p与circ_Larp4b或Mef2c之间的关系。在Ang II处理的HL-1细胞中,circ_Larp4b和Mef2c上调。此外,circ_Larp4b下调可调节Ang II诱导的CH进程。MiR-298-5p是circ_Larp4b的靶标,Mef2c是miR-298-5p的靶标。过表达的Mef2c可逆转miR-298-5p在Ang II诱导的HL-1细胞中抑制的细胞大小。Circ_Larp4b通过调节miR-298-5p/Mef2c轴来调节CH进程。

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