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MicroRNA-136-5p protects cardiomyocytes from coronary microembolization through the inhibition of pyroptosis

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Abstract

This study investigated how miR-136-5p partially affected cardiomyocyte pyroptosis in rats with coronary microembolization (CME). The cardiac function and structure of rats with CME were evaluated using echocardiography, hematoxylin and eosin staining, Masson staining, and troponin I level. Pyroptosis was induced by lipopolysaccharide (LPS) in isolated rat cardiomyocytes and evaluated by the expression of caspase-1, NOD-like receptor family pyrin domain-containing 3, interleukin-1β, and gasdermin D–N. After cell transfection, the expression of Ataxin-1 like (ATXN1L), pyrin domain-containing 1 (PYDC1), and pyroptosis-related proteins was assessed. Dual-luciferase reporter and immunoprecipitation assays were used to verify the relationships among miR-136-5p, ATXN1L, and capicua (CIC). MiR-136-5p was under-expressed, whereas ATXN1L was overexpressed in rats with CME and in LPS-treated primary cardiomyocytes. MiR-136-5p targeted ATXN1L, and ATXN1L bound to CIC to suppress PYDC1 expression. MiR-136-5p overexpression suppressed pyroptosis by inhibiting the binding of ATXN1L with CIC and promoting PYDC1 expression, which was reversed by simultaneous elevation of ATXN1L. In conclusion, miR-136-5p suppressed pyroptosis by upregulating PYDC1 via ATXN1L/CIC axis, thereby attenuating cardiac damage caused by CME.

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Data availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

Thanks for the grants from the National Natural Science Foundation of China (Grant No. 81960079), the Natural Science Foundation of Guangxi Province (Grant No. 2020GXNSFDA238007; Grant No. 2020GXNSFFA297002), The Key Research and Development Program of Guangxi (Grant No. AB20159005), Guangxi BaGui Scholars Special Project and Guangxi Health Commission Key Laboratory of Disease Proteomics Research.

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  1. Ruping Cai and Yuli Xu have contributed equally to this research.

Authors and Affiliations

  1. Department of Cardiology, Affiliated Hospital of Guilin Medical University, No. 15, Lequn Road, Guilin, 541001, Guangxi, China

    Ruping Cai, Yuli Xu, Yanling Ren, Shirong He, Quanzhong Li, Xiheng Yang, Rixin Dai & Qiang Su

  2. Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China

    Jing Zheng & Binghui Kong

  3. College of Biotechnology, Guilin Medical University, No. 1, Zhiyuan Road, Guilin, 541004, Guangxi, China

    Riming Wei

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  1. Ruping Cai
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Contributions

CRP and XYL contributed equally to the manuscript, WRM and SQ had full access to all of the data in the study and takes responsibility for the integrity of the data, the accuracy of the data analysis, RYL and HSR wrote the manuscript draft. CRP, XYL and ZJ performed research. KBH and LQZ contributed substantially to the study design and the writing of the manuscript. YXH and DRX contributed to the manuscript preparation and statistical analysis. CRP and XYL revised the manuscript. All authors read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Riming Wei or Qiang Su.

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The authors declare there is no conflict of interest regarding the publication of this paper.

Ethical approval

The experimental design complied with the implementation regulations for the management of medical experimental animals of the National Health and Planning Committee of China and the Guide for the Use and Management of Laboratory Animals of the National Institutes of Health. All study protocols were authorized by the ethics committee of Guilin Medical University.

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10495_2022_1712_MOESM1_ESM.tif

Supplementary figure 1 Note: (A) Cardiomyocyte morphology; (B) Immunofluorescence analysis of cTnI expression in rat primary cardiomyocytes. Supplementary material 1 (TIF 11578 kb)

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Cai, R., Xu, Y., Ren, Y. et al. MicroRNA-136-5p protects cardiomyocytes from coronary microembolization through the inhibition of pyroptosis. Apoptosis 27, 206–221 (2022). https://doi.org/10.1007/s10495-022-01712-5

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