MiR-489 aggravates H2O2-induced apoptosis of cardiomyocytes via inhibiting IGF1

Abstract

Myocardial infarction (MI) is a major type of cardiovascular disorder worldwide. In this study, we established a new microRNA (miRNA)-mRNA crosstalk network by integrating data obtained from The National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO). In addition, functional assays, including Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analyses, were conducted using the Database for Annotation, Visualization, and Integration Discovery (DAVID). In our study, we generated a new differentially expressed miRNA (DEmiRNA)-differentially expressed gene (DEG) crosstalk network of MI composed of 3 miRNA (miR-489, miR-375, and miR-142-3p) nodes and 163 mRNA nodes. In vitro experiments demonstrated that miR-489 expression was increased in H2O2-treated H9c2 cardiomyocytes in vitro, mimicking myocardial injury. We observed that downregulation of miR-489 reduced H2O2-induced apoptosis, while overexpression of miR-489 had the opposite effects, as revealed by flow cytometry and Western blot analyses. Furthermore, we confirmed the relationship between miR-489 and IGF1 through double luciferase reporter gene assays, which partly explains the antiapoptotic mechanism of miR-489. In conclusion, the experimental results of this study could provide important clues for investigating the mechanism of MI.

Kurarinone attenuates hydrogen peroxide‐induced oxidative stress and apoptosis through activating the PI3K/Akt signaling by upregulating IGF1 expression in human ovarian granulosa cells

“…Our study firstly confirmed that IGF1 acted as a target of kurarinone, and kurarinone upregulated IGF1 expression in H 2 O 2 ‐treated KGN cells. Previous studies suggested the protective roles of IGF1 in H 2 O 2 ‐induced cell injury in keratinocytes, hepatocytes, and cardiomyocytes 18–20 . Consistent to these reports, here we found the protective function of IGF1 against oxidative stress in granulosa cells.…”

“…Insulin‐like growth factor 1 (IGF1) is one of main regulators involving in follicle development in ovarian, 16 and it regulates ovarian function by repressing granulosa cell apoptosis 17 . Moreover, IGF1 could resist oxidative stress‐induced damage in multiple cell lines, such as keratinocytes, hepatocytes and cardiomyocytes 18–20 . However, whether IFG1 is linked to oxidative stress‐induced granulosa cell injury remains uncertain.…”

“…17 Moreover, IGF1 could resist oxidative stress-induced damage in multiple cell lines, such as keratinocytes, hepatocytes and cardiomyocytes. [18][19][20] However, whether IFG1 is linked to oxidative stress-induced granulosa cell injury remains uncertain. The phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (Akt) signaling is one common downstream signaling of IGF1, 21 and its activation protects against oxidative stress-induced damage in multiple cell lines, including granulosa cells.…”

Expression Analysis of Moritella viscosa-Challenged Atlantic Salmon Identifies Disease-Responding Genes, MicroRNAs and Their Predicted Target Genes and Pathways

“…All of these have been shown as involved in regulation of immune responses, angiogenesis, or wound healing. The three downregulated miRNAs were; miR-137 (angiogenesis and muscle regeneration [ 63 , 64 ]), miR-218 (regulation of cytokines, chemokines and interferon production, hypoxia-responding [ 65 , 66 , 67 ]) and mir-489 (apoptosis and wound healing [ 68 , 69 , 70 ]). Similarly, the three upregulated miRNAs have been reported as involved in regulation of disease relevant responses; miR-730 is an Actinopterygii-specific miRNA responding to bacterial infection in Zebrafish [ 52 , 71 , 72 ]), miR-144 regulates apoptosis/cell cycle control [ 73 ] while the teleost specific miR-2188 responds to viral infection and is likely involved in macrophage differentiation [ 25 , 74 ].…”

Modulatory Effect of Myokines on Reactive Oxygen Species in Ischemia/Reperfusion

“…Intravenous injection of IGF-1 30 min before left anterior descending artery ligation ameliorated myocardial infarct size and apoptosis [ 159 ]. Downregulation of IGF-1 during I/R through microRNA-320 and microRNA-489 aggravated the extent of myocardial infarction, ventricular remodeling, and apoptotic cell death [ 160 , 161 ], proposing an important IGF-1 mediated endogenous protection against ischemic cell death. This is further affirmed by the findings that genetic depletion of mouse mast cell protease 4—presumably responsible for endogenous IGF-1 degradation—alleviated myocardial infarct size, post-ischemic cardiac dysfunction and remodeling [ 162 ].…”