心肌circ_0010074在心肌梗死后，通过海绵化m6A修饰的miR-214-3p上调NLRP1诱导心肌炎症，促进纤维化

IF 1.7 4区综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES

Journal of Radiation Research and Applied Sciences Pub Date : 2025-06-10 DOI:10.1016/j.jrras.2025.101673

Yunhua Liu , Xiaoyu Li , Yahan Yu , Wenjuan Wang , Anqi Li , Yunliang Yao

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引用次数: 0

摘要

背景心肌梗死（MI）是一种危及生命的冠状动脉疾病，其住院死亡率高达14.7%。目前迫切需要探索新的治疗靶点和策略。尽管环状rna （circRNAs）在心肌梗死中发挥着重要作用，但关于环状rna在心肌梗死中的作用的知识有限，心肌circ_0010074对心肌梗死的影响尚不清楚。方法本研究采用小鼠原代心肌细胞和心肌成纤维细胞，将原代心肌细胞暴露于H2O2中，体外建立心肌梗死模型。此外，通过双荧光素酶报告基因法鉴定circRNA-microRNA (miRNA)-mRNA之间的调控作用，甲基化RNA免疫沉淀法（MeRIP）检测circ_0010074的n6 -甲基腺苷（m6A）修饰。结果研究表明心肌梗死后心肌circ_0010074表达上调，心肌circ_0010074诱导心肌梗死后nod样受体家族pyrin结构域1 （NLRP1）炎症和NLRP1介导的心肌纤维化，机制上circ_0010074通过海绵吸入miR-214-3p上调NLRP1表达。此外，m6A修饰可增强circ_0010074对心肌细胞中miR-214-3p的海绵作用。结论本研究提示心肌circ_0010074依赖于m6A修饰，通过海绵作用miR-214-3p增加NLRP1的表达，从而触发心肌炎症，促进心肌纤维化，这可能为挖掘更有效治疗心肌梗死的药物提供新的治疗靶点。

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Myocardial circ_0010074 induces cardiac inflammation to facilitate fibrosis by upregulating NLRP1 via sponging miR-214–3p with m6A modification after myocardial infarction

Backgrounds

Myocardial infarction (MI) is a life-threatening coronary artery disease, and the in-hospital mortality rate of MI is up to 14.7 %. It is urgent to explore novel therapeutic targets and strategies for MI. Though circular RNAs (circRNAs) play fundamental roles in MI, the knowledge about circRNAs in MI is limited, and the effect of myocardial circ_0010074 on MI remains unknown.

Methods

In this study, primary murine cardiomyocytes and cardiac fibroblasts were utilized, and primary cardiomyocytes were exposed to H₂O₂ for establishing MI model in vitro. Besides, the regulatory effects among circRNA-microRNA (miRNA)-mRNA were identified by dual-luciferase reporter gene assay, and N⁶-methyladenosine (m⁶A) modification of circ_0010074 was detected by methylated RNA Immunoprecipitation (MeRIP).

Results

The investigation indicates that myocardial circ_0010074 is upregulated after MI. Moreover, myocardial circ_0010074 induces NOD-like receptor family pyrin domain-containing 1 (NLRP1) inflammation and NLRP1-mediated cardiac fibrosis after MI. Mechanistically, myocardial circ_0010074 elevates NLRP1 expressing by sponging miR-214–3p. Besides, m⁶A modification enhances circ_0010074 to sponge miR-214–3p in cardiomyocytes after MI.

Conclusions

Our findings suggest that myocardial circ_0010074 triggers cardiac inflammation to facilitate fibrosis by increasing NLRP1 expression via sponging miR-214–3p depended on m⁶A modification after MI, which might provide novel therapeutic targets to dig more effective drugs for treating MI.

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来源期刊

Journal of Radiation Research and Applied Sciences MULTIDISCIPLINARY SCIENCES-

自引率

5.90%

发文量

130

审稿时长

16 weeks

期刊介绍： Journal of Radiation Research and Applied Sciences provides a high quality medium for the publication of substantial, original and scientific and technological papers on the development and applications of nuclear, radiation and isotopes in biology, medicine, drugs, biochemistry, microbiology, agriculture, entomology, food technology, chemistry, physics, solid states, engineering, environmental and applied sciences.