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LncRNA AZIN1-AS1 ameliorates myocardial ischemia–reperfusion injury by targeting miR-6838-5p/WNT3A axis to activate Wnt-β/catenin signaling pathway

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Abstract

Myocardial reperfusion, the effective therapy for acute myocardial infarction (AMI), commonly leads to myocardial ischemia/reperfusion (I/R) injury. The effects and functional mechanisms of LncRNA AZIN1-AS1 on myocardial I/R injury in vivo and vitro are not uncovered. In our present study, we established myocardial I/R injury model of mice and H/R injury model of cardiomyocytes and we discovered AZIN1-AS1 was decreased but miR-6838-5p was increased significantly in myocardial tissues injured by I/R treatment and H9c2 cells injured by hypoxia/reoxygenation (H/R) treatment. Silencing AZIN1-AS1 down-regulated cell viability but up-regulated apoptosis rate and CK-MB in addition LDH release of cardiomyocyte under H/R injury. However, overexpression of AZIN1-AS1 recovered abovementioned effects. Additionally, miR-6838-5p was found to be the direct target of AZIN1-AS1 and exhibited negative correlation with AZIN1-AS1. Moreover, miR-6838-5p inhibitor effectively eliminated the effects of AZIN1-AS1 knockdown on H/R-injured myocardial cells. Further experiments showed that WNT3A was the target of miR-6838-5p axis and overexpression of WNT3A also counteracted the roles of AZIN1-AS1 knockdown. Furthermore, knockdown of AZIN1-AS1 dramatically inhibited the activity of WNT-β/catenin signaling pathway, which was recovered effectively by plasmid with overexpressing WNT3A. Therefore, this study firstly revealed that LncRNA AZIN1-AS1/miR-6838 axis inhibited apoptosis by activating WNT/β-catenin pathway to protect mice or H9c2 cell from I/R-induced or H/R-induced injury respectively, which advised that AZIN1-AS1 could be regarded as a potential target for treating patients with AMI.

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Funding

This work was supported by Xiamen Science and Technology Bureau “Effect of secretory ApoJ recombinant protein on atherosclerosis after balloon injury of carotid artery in rabbits” [Grant Number: 3502Z20194075] and Science and Technology Department of Fujian Province “The mechanism of alleviating ischemia–reperfusion injury in rats with acute myocardial infarction by modified and cumulative ischemia-distance adaptation model” [Grant Number: 2018D0020].

The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was approved by the guidance of the Animal Care and Use Committee of Xiamen University and abided with the principle of the Guide for the Care and Use of Laboratory Animals.

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  1. Guoming Zhang, Licheng Ding, Guangfeng Sun, and Zhixian Liu contributed equally to the work.

Authors and Affiliations

  1. Emergency Department, Xiamen Cardiovascular Hospital, Xiamen University, Xiamen, China

    Guoming Zhang, Licheng Ding, Guangfeng Sun, Zhixian Liu, Weimei Ou & Bin Wang

  2. Ultrasonic Department, Xiamen Cardiovascular Hospital, Xiamen University, No. 2999 Jinshan Road, Huli District, Xiamen, 361009, Fujian Province, China

    Yuanyuan Sun

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  1. Guoming Zhang
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  2. Licheng Ding
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Contributions

(1) Yuanyuan Sun, Guoming Zhang, Licheng Ding, Guangfeng Sun, Zhixian Liu, Weimei Ou, and Bin Wang made substantial contributions to conception, design, acquisition of data, and analysis in addition to the interpretation of data. (2) Yuanyuan Sun, Guoming Zhang, Licheng Ding, Guangfeng Sun, and Zhixian Liu participated in drafting the article and revising it critically for important intellectual content. (3) Yuanyuan Sun gave final approval of the version to be submitted and any revised version to be published.

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Correspondence to Yuanyuan Sun.

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Conflict of interest

This work was supported by Xiamen Science and Technology Bureau “Effect of secretory ApoJ recombinant protein on atherosclerosis after balloon injury of carotid artery in rabbits” [Grant Number: 3502Z20194075] and Science and Technology Department of Fujian Province “The mechanism of alleviating ischemia–reperfusion injury in rats with acute myocardial infarction by modified and cumulative ischemia-distance adaptation model” [Grant Number: 2018D0020]. There is no other conflict of interest to declare.

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Zhang, G., Ding, L., Sun, G. et al. LncRNA AZIN1-AS1 ameliorates myocardial ischemia–reperfusion injury by targeting miR-6838-5p/WNT3A axis to activate Wnt-β/catenin signaling pathway. In Vitro Cell.Dev.Biol.-Animal 58, 54–68 (2022). https://doi.org/10.1007/s11626-022-00646-1

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  • DOI: https://doi.org/10.1007/s11626-022-00646-1

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