Molecular mechanism of Mettl14 mediated m6A modification in improving myocardial infarction
ZHENG Xuebin
SHA Sha
YANG Huiqiong
LIU Lian
Abstract：Objective To investigate the biological role of methyltransferase-like 14(METTL14)-medi-ated 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 signifi-cantly(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.
Keywords：methyltransferase-like 14N6-methyladenosinemyocardial infarctionubiquitin-specific peptidase 48
Publication Date：2023-11-10
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 2754-2760 )