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Published on: May 26, 2023
CircPAN3 ameliorates myocardial ischaemia/reperfusion injury by targeting miR-421/Pink1 axis-mediated autophagy
Cheng-Long Zhang1, Tian-Yi Long1, Si-Si Bi1
1Department of Cardiology, Xiangya Hospital, Central South University, 410008, Changsha, Hunan Province, P.R. China.
Insights
Circular RNA PAN3 (circPAN3) protects against heart injury by inhibiting cell death and autophagy. This study reveals the circPAN3-miR-421-Pink1 pathway as a potential therapeutic target for cardiovascular diseases.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- RNA Biology
Background:
- Cardiovascular diseases are the leading global cause of mortality.
- Myocardial ischemia/reperfusion (I/R) injury is a significant risk factor for cardiovascular diseases, with underlying mechanisms not fully understood.
- Understanding I/R injury pathways is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of circular RNA PAN3 (circPAN3) in myocardial I/R injury.
- To elucidate the molecular mechanisms underlying circPAN3's effects on cardiomyocyte apoptosis and autophagy.
- To identify potential therapeutic targets within the circPAN3 regulatory network.
Main Methods:
- Utilized a mouse model of myocardial I/R injury.
- Assessed circPAN3 expression levels.
- Manipulated circPAN3 expression (overexpression and knockdown) and evaluated effects on autophagy, apoptosis, and infarct size.
- Identified miR-421 as a downstream target of circPAN3 and Pink1 as a target of miR-421 using molecular biology techniques.
Main Results:
- circPAN3 expression was decreased in myocardial I/R injury.
- Overexpression of circPAN3 inhibited autophagy and alleviated cardiomyocyte apoptosis, reducing infarct size in vivo.
- circPAN3 exerted its protective effects by targeting miR-421, which in turn targets Pink1.
- Knockdown of Pink1 abolished the protective effects of circPAN3 overexpression.
Conclusions:
- circPAN3 plays a protective role in myocardial I/R injury by suppressing autophagy and apoptosis.
- The circPAN3-miR-421-Pink1 axis represents a novel regulatory network in myocardial I/R injury.
- This pathway offers potential therapeutic targets for treating cardiovascular diseases.
Abstract:
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.
