首页|Long non-coding RNA-AK138945 regulates myocardial ischemia-reperfusion injury via the miR-1-GRP94 signaling pathway

Long non-coding RNA-AK138945 regulates myocardial ischemia-reperfusion injury via the miR-1-GRP94 signaling pathway

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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.

myocardial ischemia reperfusionlncRNAapoptosismicroRNA GRP94

Yanying Wang、Jian Huang、Han Sun、Jie Liu、Yingchun Shao、Manyu Gong、Xuewen Yang、Dongping Liu、Zhuo Wang、Haodong Li、Yanwei Zhang、Xiyang Zhang、Zhiyuan Du、Xiaoping Leng、Lei Jiao、Ying Zhang

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State Key Laboratory of Frigid Zone Cardiovascular Diseases,and Pharmacology Department of Pharmacy college of Harbin Medical University,Harbin 150081,China

The Fourth Department of Medical Oncology,Harbin Medical University Cancer Hospital,Harbin 150040,China

Cancer Institute,The Affiliated Hospital of Qingdao University,Qingdao University,Qingdao Cancer Institute,Qingdao 266071,China

College of Bioinformatics Science and Technology,Harbin Medical University,Harbin 150081,China

Department of Ultrasound Imaging,the Second Affiliated Hospital of Harbin Medical University,Harbin 150086,China

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国家自然科学基金国家自然科学基金国家自然科学基金Certificate of China Postdoctoral Science Foundation Grantpostdoctoral funding from Heilongjiang ProvinceHai Yan Youth Fund from Harbin Medical University Cancer Hospital

8237041781970320822702732021M69382621042230046JJQN2021-09

2024

10.2478/fzm-2024-0004

寒地医学(英文)
黑龙江省卫生健康发展研究中心

寒地医学(英文)

ISSN：2096-9074
年,卷(期)：2024.4(1)
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