CircPAN3 ameliorates myocardial ischaemia/reperfusion injury by targeting miR-421/Pink1 axis-mediated autophagy suppression


Cardiovascular diseases are considered the leading cause of death worldwide. Myocardial ischaemia/reperfusion (I/R) injury is recognized as a critical risk factor for cardiovascular diseases. Although increasing advances have been made recently in understanding the mechanisms of I/R injury, they remain largely unknown. In this study, we found that the expression of circPAN3 (circular RNA PAN3) was decreased in a mouse model of myocardial I/R. Overexpression of circPAN3 significantly inhibited autophagy and alleviated cell apoptosis of cardiomyocytes, which was further verified in vivo by decreased autophagic vacuoles and reduced myocardial infarct sizes. Moreover, miR-421 (microRNA-421) was identified as a downstream target involved in circPAN3-mediated myocardial I/R injury. Additionally, miR-421 could negatively regulate Pink1 (phosphatase and tensin homologue-induced putative kinase 1) via a direct binding relationship. Furthermore, the mitigating effects of circPAN3 overexpression on myocardial I/R injury by suppressing autophagy and apoptosis were abolished by knockdown of Pink1. Our findings reveal a novel role for circPAN3 in modulating autophagy and apoptosis in myocardial I/R injury and the circPAN3–miR-421–Pink1 axis as a regulatory network, which might provide potential therapeutic targets for cardiovascular diseases.

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Fig. 1: Enhanced autophagy and downregulation of circPAN3 were observed in the mouse model of myocardial I/R injury.
Fig. 2: Overexpression of circPAN3 alleviated myocardial I/R injury and inhibited autophagy.
Fig. 3: CircPAN3 relieved H/R-induced myocardial damage and suppressed autophagy and apoptosis.
Fig. 4: CircPAN3 acts as a sponge of miR-421.
Fig. 5: miR-421 reversed the protective effects of circPAN3 on H/R-induced cardiomyocyte damage.
Fig. 6: Pink1 was a direct target of miR-421.
Fig. 7: CircPAN3 regulated myocardial I/R injury by targeting the miR-421/Pink1 axis.


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This work was supported by Hunan Provincial Natural Science Foundation Youth Fund (No. 2020JJ5945).

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Guarantor of integrity of the entire study, study concepts, study design and manuscript review: FL. Definition of intellectual content and literature research: S-SB. Experimental studies and manuscript preparation: C-LZ and T-YL. Data acquisition: C-LZ. Data analysis: C-LZ and SAS. Statistical analysis: T-YL. Manuscript editing: SAS.

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Correspondence to Fei Li.

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Zhang, C., Long, T., Bi, S. et al. CircPAN3 ameliorates myocardial ischaemia/reperfusion injury by targeting miR-421/Pink1 axis-mediated autophagy suppression. Lab Invest (2020).

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