Title:MicroRNA-16-5p Aggravates Myocardial Infarction Injury by Targeting the Expression of Insulin Receptor Substrates 1 and Mediating Myocardial Apoptosis and Angiogenesis
VOLUME: 17 ISSUE: 1
Author(s):Xiancan Wang, Yuqiang Shang*, Shilin Dai, Wei Wu, Fan Yi and Long Cheng
Affiliation:Department of Cardiovascular Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430014, Department of Cardiovascular Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430014, Department of Cardiovascular Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430014, Department of Cardiovascular Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430014, Department of Cardiovascular Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430014, Department of Cardiovascular Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430014
Keywords:miR-16-5p, IRS1, apoptosis, angiogenesis, myocardial infarction, vascular endothelial growth factor, cardiovascular
disease.
Abstract:
Purpose: Myocardial infarction is a common cardiovascular disease. MicroRNA-16-5p
(miR-16-5p) was upregulated in heart and kidney hypoxia/reoxygenation (H/R) injury. However,
the role of miR-16-5p in myocardial infarction injury is still unclear.
Methods: Human adult ventricular cardiomyocytes (AC16) were treated with ischemia/reperfusion
(H/R). The miR-16-5p level was evaluated through real-time PCR. The activity of lactate dehydrogenase
(LDH) and creatine kinase-MB (CK-MB) was detected via LDH and CK-MB monitoring
kits. Cell viability was examined with 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetra-zolium
bromide (MTT) assay. Western blotting was used to analyze the protein levels. The luci-ferase report
assay confirmed the relative luciferase activity.
Results: miR-16-5p was elevated in H/R-treated AC16 cells. miR-16-5p overexpression and
knockdown were carried out. miR-16-5p knockdown repressed cell apoptosis, attenuated LDH and
CK-MB activities, and enhanced cell viability in H/R-treated AC16 cells. Moreover, miR-16-5p
knockdown promoted angiogenesis in human microvascular endothelial cells (HMVEC), causing
elevation of vascular endothelial growth factor (VEGF), insulin receptor substrates 1 (IRS1),
minichromosome maintenance complex component 2 (MCM2) and proliferating cell nuclear antigen
(PCNA) protein levels. Moreover, miR-16-5p was testified to target IRS1. IRS1 silencing
alleviated miR-16-5p knockdown-mediated inhibition of apoptosis in AC16 cells.
Conclusion: miR-16-5p knockdown increased cell viability and angiogenesis, as well as inhibited
cell apoptosis by increasing IRS1. These findings indicated that miR-16-5p knockdown may be a
new therapeutic target for myocardial infarction.
