{"title":"敲低circRNA_0030042通过miR-568/PRG4途径减轻心力衰竭","authors":"Li-li Wang, Hong-mei Yao, Xing-xing Zhao, Xiao-wei Yin, Jin-sheng Tian","doi":"10.1002/jbt.70267","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Heart failure is a common heart disease and cause of death globally which is caused by structural and functional abnormalities. circRNA_0030042 is a newly discovered circRNA that derived from its host gene forkhead box O1 (FOXO1). However, the role of circRNA_0030042 in heart failure is not revealed. This study aims to explore the role of circRNA_0030042 in heart failure progression. In this study, AC16 cell heart failure model was induced in a medium containing 200 µM H<sub>2</sub>O<sub>2</sub>. circRNA_0030042 was markedly elevated in peripheral blood from patients with heart failure and H<sub>2</sub>O<sub>2</sub>-induced AC16 cells. Knockdown of hsa-circRNA_0030042 repressed the apoptosis of H<sub>2</sub>O<sub>2</sub>-induced AC16 cells and facilitated the viability of H<sub>2</sub>O<sub>2</sub>-induced AC16 cells. Besides, knockdown of hsa-circRNA_0030042 decreased iron ion level, ferroptotic markers ROS and MDA levels, increased GSH level, ferroptosis-associated proteins SLC7A11 and GPX4 protein expressions in H<sub>2</sub>O<sub>2</sub>-induced AC16 cells. In addition, hsa-circRNA_0030042 could interact with miR-568, and negatively modulate miR-568 expression in AC16 cells. miR-568 also targeted PRG4, and negatively modulated PRG4 expression. hsa-circRNA_0030042 positively regulated PRG4 via miR-568 in AC16 cells. Furthermore, knockdown of circRNA_0030042 promoted the proliferation, repressed the iron ion level, ROS level, increased SLC7A11 and GPX4 protein expressions in H<sub>2</sub>O<sub>2</sub>-induced AC16 cells via miR-568/PRG4 pathway. Finally, transverse aortic constriction (TAC) mice model were conducted by a thoracotomy procedure under the microscope. In vivo experiments showed that knockdown of mmu-circRNA_0030042 ameliorated cardiac dysfunction, decreased myocardial injury markers cTnI, CK-MB and BNP levels, relieved cardiac histopathological damage, decreased the apoptosis of heart tissue, and increased GSH, SLC7A11 and GPX4 protein expressions in heart tissue of TAC mice. Therefore, knockdown of circRNA_0030042 attenuated heart failure via miR-568/PRG4 pathway.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Knockdown of circRNA_0030042 Attenuates Heart Failure via miR-568/PRG4 Pathway\",\"authors\":\"Li-li Wang, Hong-mei Yao, Xing-xing Zhao, Xiao-wei Yin, Jin-sheng Tian\",\"doi\":\"10.1002/jbt.70267\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>Heart failure is a common heart disease and cause of death globally which is caused by structural and functional abnormalities. circRNA_0030042 is a newly discovered circRNA that derived from its host gene forkhead box O1 (FOXO1). However, the role of circRNA_0030042 in heart failure is not revealed. This study aims to explore the role of circRNA_0030042 in heart failure progression. In this study, AC16 cell heart failure model was induced in a medium containing 200 µM H<sub>2</sub>O<sub>2</sub>. circRNA_0030042 was markedly elevated in peripheral blood from patients with heart failure and H<sub>2</sub>O<sub>2</sub>-induced AC16 cells. Knockdown of hsa-circRNA_0030042 repressed the apoptosis of H<sub>2</sub>O<sub>2</sub>-induced AC16 cells and facilitated the viability of H<sub>2</sub>O<sub>2</sub>-induced AC16 cells. Besides, knockdown of hsa-circRNA_0030042 decreased iron ion level, ferroptotic markers ROS and MDA levels, increased GSH level, ferroptosis-associated proteins SLC7A11 and GPX4 protein expressions in H<sub>2</sub>O<sub>2</sub>-induced AC16 cells. In addition, hsa-circRNA_0030042 could interact with miR-568, and negatively modulate miR-568 expression in AC16 cells. miR-568 also targeted PRG4, and negatively modulated PRG4 expression. hsa-circRNA_0030042 positively regulated PRG4 via miR-568 in AC16 cells. Furthermore, knockdown of circRNA_0030042 promoted the proliferation, repressed the iron ion level, ROS level, increased SLC7A11 and GPX4 protein expressions in H<sub>2</sub>O<sub>2</sub>-induced AC16 cells via miR-568/PRG4 pathway. Finally, transverse aortic constriction (TAC) mice model were conducted by a thoracotomy procedure under the microscope. In vivo experiments showed that knockdown of mmu-circRNA_0030042 ameliorated cardiac dysfunction, decreased myocardial injury markers cTnI, CK-MB and BNP levels, relieved cardiac histopathological damage, decreased the apoptosis of heart tissue, and increased GSH, SLC7A11 and GPX4 protein expressions in heart tissue of TAC mice. Therefore, knockdown of circRNA_0030042 attenuated heart failure via miR-568/PRG4 pathway.</p></div>\",\"PeriodicalId\":15151,\"journal\":{\"name\":\"Journal of Biochemical and Molecular Toxicology\",\"volume\":\"39 5\",\"pages\":\"\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2025-04-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Biochemical and Molecular Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jbt.70267\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biochemical and Molecular Toxicology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jbt.70267","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Knockdown of circRNA_0030042 Attenuates Heart Failure via miR-568/PRG4 Pathway
Heart failure is a common heart disease and cause of death globally which is caused by structural and functional abnormalities. circRNA_0030042 is a newly discovered circRNA that derived from its host gene forkhead box O1 (FOXO1). However, the role of circRNA_0030042 in heart failure is not revealed. This study aims to explore the role of circRNA_0030042 in heart failure progression. In this study, AC16 cell heart failure model was induced in a medium containing 200 µM H2O2. circRNA_0030042 was markedly elevated in peripheral blood from patients with heart failure and H2O2-induced AC16 cells. Knockdown of hsa-circRNA_0030042 repressed the apoptosis of H2O2-induced AC16 cells and facilitated the viability of H2O2-induced AC16 cells. Besides, knockdown of hsa-circRNA_0030042 decreased iron ion level, ferroptotic markers ROS and MDA levels, increased GSH level, ferroptosis-associated proteins SLC7A11 and GPX4 protein expressions in H2O2-induced AC16 cells. In addition, hsa-circRNA_0030042 could interact with miR-568, and negatively modulate miR-568 expression in AC16 cells. miR-568 also targeted PRG4, and negatively modulated PRG4 expression. hsa-circRNA_0030042 positively regulated PRG4 via miR-568 in AC16 cells. Furthermore, knockdown of circRNA_0030042 promoted the proliferation, repressed the iron ion level, ROS level, increased SLC7A11 and GPX4 protein expressions in H2O2-induced AC16 cells via miR-568/PRG4 pathway. Finally, transverse aortic constriction (TAC) mice model were conducted by a thoracotomy procedure under the microscope. In vivo experiments showed that knockdown of mmu-circRNA_0030042 ameliorated cardiac dysfunction, decreased myocardial injury markers cTnI, CK-MB and BNP levels, relieved cardiac histopathological damage, decreased the apoptosis of heart tissue, and increased GSH, SLC7A11 and GPX4 protein expressions in heart tissue of TAC mice. Therefore, knockdown of circRNA_0030042 attenuated heart failure via miR-568/PRG4 pathway.
期刊介绍：
The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
