The Journal of Practical Medicine >

2023 , Vol. 39 >Issue 21: 2754 - 2760

DOI: https://doi.org/10.3969/j.issn.1006-5725.2023.21.011

Basic Research

Molecular mechanism of Mettl14 mediated m6A modification in improving myocardial infarction

  • Xuebin ZHENG ,
  • Sha SHA ,
  • Huiqiong YANG ,
  • Lian LIU
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  • Department of General Practice，Changsha Fourth Hospital （Changsha Hospital Affiliated to Hunan Normal University），Changsha 410006，China

Received date: 2023-05-14

  Online published: 2023-12-19

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Abstract

Objective To investigate the biological role of methyltransferase-like 14 （METTL14）-mediated m6A modification in myocardial infarction （MI）. Methods A total of 40 mice were randomly divided into 4 groups： Sham+AAV9-NC group （n = 10）， Sham+AAV9-METTL14 group （n = 10）， MI+AAV9-NC group （n = 10） and MI+AAV9-METTL14 group （n = 10）. Mice in each group were injected with AAV9-METTL14 or AAV9-NC through the tail vein one week before MI induction. Cardiac function was measured non-invasively by transthoracic echocardiography， and microvascular injury were measured by immunofluorescence. CMECs were isolated from mouse myocardial tissue， and the cells were treated with oxygen-glucose deprivation （OGD）. Results METTL14 was downregulated in MI mouse heart tissue as well as in OGD-treated CMECs. Compared with the Sham+AAV9-NC group， the expression of VE-cadherin was significantly down-regulated （P < 0.05）， ROS levels increased significantly （P < 0.05） in the MI+AAV9-NC group. MI+AAV9-METTL14 suppressed these changes and enhanced cardiac function in mice. Compared with the NC group， a significant increase in mitochondrial ROS levels was observed in the OGD group （P < 0.05）. Knockdown of METTL14 in CMECs exacerbated ROS levels （P < 0.05）， and the addition of USP48 overexpression plasmid reversed these changes （P < 0.05）. Conclusion METTL14 was lowly expressed in MI and mediates mitochondrial dysfunction in CMECs by increasing the m6A modification level of USP48 in CMECs to reduce its stability.

Key words： methyltransferase-like 14; N6-methyladenosine; myocardial infarction; ubiquitin-specific peptidase 48

Cite this article

Xuebin ZHENG , Sha SHA , Huiqiong YANG , Lian LIU . Molecular mechanism of Mettl14 mediated m6A modification in improving myocardial infarction[J]. The Journal of Practical Medicine, 2023 , 39(21) : 2754 -2760 . DOI: 10.3969/j.issn.1006-5725.2023.21.011

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