Long non-coding RNA-AK138945 regulates myocardial ischemia-reperfusion injury via the miR-1-GRP94 signaling pathway
Yanying Wang1
Jian Huang2
Han Sun1
Jie Liu1
Yingchun Shao3
Manyu Gong4
Xuewen Yang1
Dongping Liu1
Zhuo Wang5
Haodong Li1
Yanwei Zhang1
Xiyang Zhang1
Zhiyuan Du1
Xiaoping Leng5
Lei Jiao1
Ying Zhang1
1.State Key Laboratory of Frigid Zone Cardiovascular Diseases,and Pharmacology Department of Pharmacy college of Harbin Medical University,Harbin 150081,China2.The Fourth Department of Medical Oncology,Harbin Medical University Cancer Hospital,Harbin 150040,China3.State Key Laboratory of Frigid Zone Cardiovascular Diseases,and Pharmacology Department of Pharmacy college of Harbin Medical University,Harbin 150081,China;Cancer Institute,The Affiliated Hospital of Qingdao University,Qingdao University,Qingdao Cancer Institute,Qingdao 266071,China4.State Key Laboratory of Frigid Zone Cardiovascular Diseases,and Pharmacology Department of Pharmacy college of Harbin Medical University,Harbin 150081,China;College of Bioinformatics Science and Technology,Harbin Medical University,Harbin 150081,China5.Department of Ultrasound Imaging,the Second Affiliated Hospital of Harbin Medical University,Harbin 150086,China
摘要：Objective:Myocardial ischemia-reperfusion injury(MIRI)is one of the leading causes of death from cardiovascular disease in humans,especially in individuals exposed to cold environments.Long non-coding RNAs(lncRNAs)regulate MIRI through multiple mechanisms.This study explored the regulatory effect of lncRNA-AK138945 on myocardial ischemia-reperfusion injury and its mechanism.Methods:In vivo,8-to 12-weeks-old C57BL/6 male mice underwent ligation of the left anterior descending coronary artery for 50 minutes followed by reperfusion for 48 hours.In vitro,the primary cultured neonatal mouse ventricular cardiomyocytes(NMVCs)were treated with 100 μmol/L hydrogen peroxide(H2O2).The knockdown of lncRNA-AK138945 was evaluated to detect cardiomyocyte apoptosis,and a glucose-regulated,endoplasmic reticulum stress-related protein 94(GRP94)inhibitor was used to detect myocardial injury.Results:We found that the expression level of lncRNA-AK138945 was reduced in MIRI mouse heart tissue and H2O2-treated cardiomyocytes.Moreover,the proportion of apoptosis in cardiomyocytes increased after lncRNA-AK138945 was silenced.The expression level of Bcl2 protein was decreased,and the expression level of Bad,Caspase 9 and Caspase 3 protein was increased.Our further study found that miR-1a-3p is a direct target of lncRNA-AK138945,after lncRNA-AK138945 was silenced in cardiomyocytes,the expression level of miR-1a-3p was increased while the expression level of its downstream protein GRP94 was decreased.Interestingly,treatment with a GRP94 inhibitor(PU-WS13)intensified H2O2-induced cardiomyocyte apoptosis.After overexpression of FOXO3,the expression levels of lncRNA-AK138945 and GRP94 were increased,while the expression levels of miR-1a-3p were decreased.Conclusion:LncRNA-AK138945 inhibits GRP94 expression by regulating miR-1a-3p,leading to cardiomyocyte apoptosis.The transcription factor Forkhead Box Protein O3(FOXO3)participates in cardiomyocyte apoptosis induced by endoplasmic reticulum stress through up-regulation of lncRNA-AK138945.
机标关键词：ischemiapathwaylonginjurymyocardialnon-codingregulatesreperfusion
论文发表日期：2024-01-30
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：11( 31-40,中插4 )
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