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Possible implication of miR-142-3p in coronary microembolization induced myocardial injury via ATXN1L/HDAC3/NOL3 axis

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Abstract

This study aims to explore the mechanism underlying miR-142-3p regulating myocardial injury induced by coronary microembolization (CME) through ATXN1L. miR-142-3p overexpression or ATXN1L knockout adenovirus vectors were injected into rats before CME treatment. Cardiac functions were examined by echocardiography, and pathologies of myocardial tissues were assessed. Then, serum cTnI and IL-1β contents and concentrations of IL-1β and IL-18 in cell supernatant were measured. Immunofluorescence determined the localization of histone deacetylase 3 (HDAC3). The interaction between miR-142-3p and ATXN1L as well as the binding between HDAC3 and histone 3 (H3) was identified. The binding of ATXN1L and HDAC3 to NOL3 promoter was verified using ChIP. The levels of ATXN1L, NOL3, and miR-142-3p as well as apoptosis- and pyroptosis-related proteins and acetyl-histone 3 (ac-H3) were evaluated. CME treatment impaired the cardiac functions in rats and increased cTnI content. CME rats showed microinfarction foci in myocardial tissues. After CME treatment, miR-142-3p and NOL3 were modestly expressed while ATXN1L content was elevated, in addition to increases in apoptosis and pyroptosis. miR-142-3p overexpression or ATXN1L knockout alleviated CME-induced myocardial injury, cardiomyocyte apoptosis, and pyroptosis in myocardial tissues. miR-142-3p regulated ATXN1L expression in a targeted manner. In the cellular context, miR-142-3p overexpression attenuated apoptosis and pyroptosis in cardiomyocytes, which was partly counteracted by ATXN1L overexpression. ATXN1L functioned on cardiomyocytes by promoting deacetylation of H3 through HDAC3 and thus inhibited NOL3 expression. Inhibition of HDAC3 or overexpression of NOL3 ameliorated the promotive effects of ATXN1L on cardiomyocyte apoptosis and pyroptosis. In vivo and in vitro evidence in this study supported that miR-142-3p could attenuate CME-induced myocardial injury via ATXN1L/HDAC3/NOL3.

Highlights

  • CME model witnessed aberrant expression of miR-142-3p, ATXN1L, and NOL3;

  • miR-142-3p negatively regulated ATXN1L;

  • miR-142-3p mediated CME-induced myocardial injury through ATXN1L;

  • ATXN1L promoted deacetylation of H3 through HDAC3 and thus inhibited NOL3 expression;

  • ATXN1L acted on cardiomyocyte apoptosis and pyroptosis through HDAC3/NOL3 axis.

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Data availability

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

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Acknowledgements

Thanks for all the support and contributions of the participators.

Funding

This research was funded by the grants from the National Natural Science Foundation of China (Grant No. 81960079); Guangxi Natural Science Foundation (Grant No. 2020GXNSFDA238007; Grant No. 2020GXNSFFA297002; Grant No. 2020GXNSFAA297009); 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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Authors and Affiliations

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

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

  2. Department of Radiology, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, 541001, People’s Republic of China

    Wei Zhang

  3. School of Intelligent Medicine and Biotechbology, Guilin Medical University, Lingui District, No.1, Zhiyuan Road, Guilin, Guangxi, 541199, People’s Republic of China

    Riming Wei

  4. Guangxi Health Commission Key Laboratory of Disease Proteomics Research, Guilin, Guangxi, 541199, People’s Republic of China

    Qiang Su

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  1. Yuli Xu
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Contributions

Yuli Xu: Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Writing–original draft. Xiangwei Lv: Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Writing–original draft. Ruping Cai: Data curation, Formal analysis, Investigation, Methodology. Yanling Ren: Methodology. Rixin Dai: Methodology. Shirong He: Resources. Wei Zhang: Supervision. Quanzhong Li: Methodology, Writing–original draft. Xiheng Yang: Data curation, Formal analysis. Qiang Su: Conceptualization, Formal analysis, Supervision, Funding acquisition, Validation, Project administration, Writing–review and editing. Riming Wei: Conceptualization, Supervision, Funding acquisition, Validation, Project administration, Writing–review and editing.

Corresponding authors

Correspondence to Riming Wei or Qiang Su.

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Ethics approval and consent to participate

All experiments were approved by Guilin Medical University and produced in line with the guidance for the care and use of laboratory animals issued by National Institutes of Health (NIH). All efforts had been made to minimize pain in animals.

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The authors declare no competing interests.

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Yuli Xu and Xiangwei Lv contributed equally to this research.

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Xu, Y., Lv, X., Cai, R. et al. Possible implication of miR-142-3p in coronary microembolization induced myocardial injury via ATXN1L/HDAC3/NOL3 axis. J Mol Med 100, 763–780 (2022). https://doi.org/10.1007/s00109-022-02198-z

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