Xiaoling Li, Longwei Zhou, Chengyan Yang, Keqin Wang, Yangjie Li, Sha Han, Xuan Gong, Ke Qin, Zengxue Lu
{"title":"The m6A methyltransferase METTL14 governs NLRP3 and facilitates myocardial infarction via pyroptosis.","authors":"Xiaoling Li, Longwei Zhou, Chengyan Yang, Keqin Wang, Yangjie Li, Sha Han, Xuan Gong, Ke Qin, Zengxue Lu","doi":"10.1177/13860291251352301","DOIUrl":null,"url":null,"abstract":"<p><p>BackgroundN6-methyladenosine (m6A) methylation plays an important role in myocardial infarction, which is related to cardiomyocyte pyroptosis. This study aimed to explore the effects of the m6A methyltransferase, METTL14, on pyroptosis and the underlying mechanisms.Materials and methodsThe role of METTL14 <i>in vivo</i> was assessed by TTC staining, biochemical indicators, and H&E assays. Cell pyroptosis was evaluated by PI staining, IF, and western blot assay. The m6A methylation of NLRP3 was evaluated by RIP, dual-luciferase reporter assay, Me-RIP, and stability test.ResultsThe results indicated that METTL14 was highly expressed in LAD-ligated mice and OGD-induced cardiomyocytes. Depletion of METTL14 inhibited OGD-induced pyroptosis of cardiomyocytes and suppressed myocardial injury. Mechanically, METTL14 promoted m6A methylation of NLRP3 to enhance mRNA stability. Overexpression of NLRP3 reversed the effects of METTL14 knockdown on pyroptosis.ConclusionsMETTL14 knockdown attenuated cardiomyocyte pyroptosis and myocardial infarction by suppressing NLRP3 m6A methylation. The findings suggested that METTL14 has the potential to be the therapeutic target of myocardial infarction.</p>","PeriodicalId":93943,"journal":{"name":"Clinical hemorheology and microcirculation","volume":" ","pages":"95-104"},"PeriodicalIF":0.0000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical hemorheology and microcirculation","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/13860291251352301","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/8 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
BackgroundN6-methyladenosine (m6A) methylation plays an important role in myocardial infarction, which is related to cardiomyocyte pyroptosis. This study aimed to explore the effects of the m6A methyltransferase, METTL14, on pyroptosis and the underlying mechanisms.Materials and methodsThe role of METTL14 in vivo was assessed by TTC staining, biochemical indicators, and H&E assays. Cell pyroptosis was evaluated by PI staining, IF, and western blot assay. The m6A methylation of NLRP3 was evaluated by RIP, dual-luciferase reporter assay, Me-RIP, and stability test.ResultsThe results indicated that METTL14 was highly expressed in LAD-ligated mice and OGD-induced cardiomyocytes. Depletion of METTL14 inhibited OGD-induced pyroptosis of cardiomyocytes and suppressed myocardial injury. Mechanically, METTL14 promoted m6A methylation of NLRP3 to enhance mRNA stability. Overexpression of NLRP3 reversed the effects of METTL14 knockdown on pyroptosis.ConclusionsMETTL14 knockdown attenuated cardiomyocyte pyroptosis and myocardial infarction by suppressing NLRP3 m6A methylation. The findings suggested that METTL14 has the potential to be the therapeutic target of myocardial infarction.
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