{"title":"miRNA-148a-3p 靶向调节脂质代谢基因 SOCS3 以减轻心肌缺血再灌注损伤。","authors":"Changgan Mo, Xiuge Tang, Ying Wei, Hui Han, Guangsuo Wei, Liyuan Wei, Xu Lin","doi":"10.23736/S2724-5683.24.06578-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Acute myocardial infarction (AMI) is a major cause of death in cardiovascular patients. SOCS3's protective role in cardiac I/R-I is being explored, and miRNAs, particularly miRNA-148a-3p, are suspected to target SOCS3. To elucidate the role of miRNA-148a-3p targeting lipid metabolism gene SOCS3 in cardiac ischemia-reperfusion injury (I/R-I) in rats.</p><p><strong>Methods: </strong>Derived mRNA expression data GSE59867 from GEO, identified 558 lipid metabolism genes from KEGG and GSEA, and screened for differentially expressed genes in acute myocardial infarction (AMI). Predicted miRNA-148a-3p targeting SOCS3 using TargetScanHuman, validated binding via luciferase assay and 3'UTR mutation. Established a rat I/R-I model to assess miRNA-148a-3p and SOCS3 expression, and investigated SOCS3 regulation by miRNA-148a-3p overexpression. Analyzed expression of NF-κB p65, IL-1β, and TNF-α-related proteins, and evaluated cardiac hemodynamics post-SOCS3 regulation by miRNA-148a-3p.</p><p><strong>Results: </strong>In GSE59867, TSPO, SOCS3, LRP1, PLB1, CYP1B1, PPARG, ACSL1, and CYP27A1 were identified as differentially expressed lipid metabolism genes in AMI. The results of immune infiltration showed a close relationship between the differential lipid metabolism genes and the infiltration of immune cells such as macrophages and monocytes. The random forest algorithm identified SOCS3 as the key gene. The luciferase reporter gene demonstrated the participation of miRNA-148a-3p in the regulation of SOCS3 by binding to its 3'UTR. In vivo experiments revealed low expression of miRNA-148a-3p in myocardial I/R, while SOCS3 was highly expressed. Elevated miRNA-148a-3p expression led to a decrease in SOCS3, NF-κB p65, IL-1β, and TNF-α levels during cardiac I/R-I. Overexpression of miRNA-148a-3p enhanced the cardiac performance in rats experiencing cardiac I/R-I.</p><p><strong>Conclusions: </strong>Overexpression of miRNA-148a-3p regulates NF-κB signaling pathway by targeting lipid metabolism gene SOCS3, reduces inflammatory response, and then reduces cardiac I/R-I in rats.</p>","PeriodicalId":18668,"journal":{"name":"Minerva cardiology and angiology","volume":" ","pages":""},"PeriodicalIF":1.4000,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"miRNA-148a-3p targets to regulate the lipid metabolism gene SOCS3 to reduce myocardial ischemia/reperfusion injury.\",\"authors\":\"Changgan Mo, Xiuge Tang, Ying Wei, Hui Han, Guangsuo Wei, Liyuan Wei, Xu Lin\",\"doi\":\"10.23736/S2724-5683.24.06578-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Acute myocardial infarction (AMI) is a major cause of death in cardiovascular patients. SOCS3's protective role in cardiac I/R-I is being explored, and miRNAs, particularly miRNA-148a-3p, are suspected to target SOCS3. To elucidate the role of miRNA-148a-3p targeting lipid metabolism gene SOCS3 in cardiac ischemia-reperfusion injury (I/R-I) in rats.</p><p><strong>Methods: </strong>Derived mRNA expression data GSE59867 from GEO, identified 558 lipid metabolism genes from KEGG and GSEA, and screened for differentially expressed genes in acute myocardial infarction (AMI). Predicted miRNA-148a-3p targeting SOCS3 using TargetScanHuman, validated binding via luciferase assay and 3'UTR mutation. Established a rat I/R-I model to assess miRNA-148a-3p and SOCS3 expression, and investigated SOCS3 regulation by miRNA-148a-3p overexpression. Analyzed expression of NF-κB p65, IL-1β, and TNF-α-related proteins, and evaluated cardiac hemodynamics post-SOCS3 regulation by miRNA-148a-3p.</p><p><strong>Results: </strong>In GSE59867, TSPO, SOCS3, LRP1, PLB1, CYP1B1, PPARG, ACSL1, and CYP27A1 were identified as differentially expressed lipid metabolism genes in AMI. The results of immune infiltration showed a close relationship between the differential lipid metabolism genes and the infiltration of immune cells such as macrophages and monocytes. The random forest algorithm identified SOCS3 as the key gene. The luciferase reporter gene demonstrated the participation of miRNA-148a-3p in the regulation of SOCS3 by binding to its 3'UTR. In vivo experiments revealed low expression of miRNA-148a-3p in myocardial I/R, while SOCS3 was highly expressed. Elevated miRNA-148a-3p expression led to a decrease in SOCS3, NF-κB p65, IL-1β, and TNF-α levels during cardiac I/R-I. Overexpression of miRNA-148a-3p enhanced the cardiac performance in rats experiencing cardiac I/R-I.</p><p><strong>Conclusions: </strong>Overexpression of miRNA-148a-3p regulates NF-κB signaling pathway by targeting lipid metabolism gene SOCS3, reduces inflammatory response, and then reduces cardiac I/R-I in rats.</p>\",\"PeriodicalId\":18668,\"journal\":{\"name\":\"Minerva cardiology and angiology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2024-11-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Minerva cardiology and angiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.23736/S2724-5683.24.06578-5\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Minerva cardiology and angiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.23736/S2724-5683.24.06578-5","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
miRNA-148a-3p targets to regulate the lipid metabolism gene SOCS3 to reduce myocardial ischemia/reperfusion injury.
Background: Acute myocardial infarction (AMI) is a major cause of death in cardiovascular patients. SOCS3's protective role in cardiac I/R-I is being explored, and miRNAs, particularly miRNA-148a-3p, are suspected to target SOCS3. To elucidate the role of miRNA-148a-3p targeting lipid metabolism gene SOCS3 in cardiac ischemia-reperfusion injury (I/R-I) in rats.
Methods: Derived mRNA expression data GSE59867 from GEO, identified 558 lipid metabolism genes from KEGG and GSEA, and screened for differentially expressed genes in acute myocardial infarction (AMI). Predicted miRNA-148a-3p targeting SOCS3 using TargetScanHuman, validated binding via luciferase assay and 3'UTR mutation. Established a rat I/R-I model to assess miRNA-148a-3p and SOCS3 expression, and investigated SOCS3 regulation by miRNA-148a-3p overexpression. Analyzed expression of NF-κB p65, IL-1β, and TNF-α-related proteins, and evaluated cardiac hemodynamics post-SOCS3 regulation by miRNA-148a-3p.
Results: In GSE59867, TSPO, SOCS3, LRP1, PLB1, CYP1B1, PPARG, ACSL1, and CYP27A1 were identified as differentially expressed lipid metabolism genes in AMI. The results of immune infiltration showed a close relationship between the differential lipid metabolism genes and the infiltration of immune cells such as macrophages and monocytes. The random forest algorithm identified SOCS3 as the key gene. The luciferase reporter gene demonstrated the participation of miRNA-148a-3p in the regulation of SOCS3 by binding to its 3'UTR. In vivo experiments revealed low expression of miRNA-148a-3p in myocardial I/R, while SOCS3 was highly expressed. Elevated miRNA-148a-3p expression led to a decrease in SOCS3, NF-κB p65, IL-1β, and TNF-α levels during cardiac I/R-I. Overexpression of miRNA-148a-3p enhanced the cardiac performance in rats experiencing cardiac I/R-I.
Conclusions: Overexpression of miRNA-148a-3p regulates NF-κB signaling pathway by targeting lipid metabolism gene SOCS3, reduces inflammatory response, and then reduces cardiac I/R-I in rats.
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