Significant role and mechanism of microRNA-143-3p/KLLN axis in the development of coronary heart disease.
AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH(2019)
摘要
Cardiovascular disease predominantly includes coronary heart disease (CHD) and stroke, results in high morbidity and mortality. MicroRNA-143-3p (miR-143-3p) is a tumor suppressor and is involved in many cancers. However, the role and mechanism of miR-143-3p in coronary heart disease is still unclear. In this study, we identified that miR-143-3p was up-regulated in rabbit CHD model. The results of TargetScan and the dual luciferase reporter assay indicated that KLLN (killin, p53 regulated DNA replication inhibitor) was a direct target of miR-143-3p. Besides, we revealed that KLLN was down-regulated in rabbit coronary heart disease model. In addition, we found that the related-markers of CHD such as TC (total cholesterol), TG (triglyceride), and LDLC (low-density lipoprotein cholesterol) in the model group were significantly increased than that in the control group. And compared with the model group, miR 143 3p inhibitor significantly reduced TC, TG, LDLC expression, while miR-143-3p mimic further increased the expression of TC, TG, and LDLC. We next found that miR-143-3p mimic promoted cell viability and migration of vascular smooth muscle cells, inhibited apoptosis; and these changes were reversed by KLLN-plasmid. And miR-143-3p inhibitor had the counter effects. Our study provided a new target for the treatment of CHD and deserves further study.
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关键词
Coronary heart disease,vascular smooth muscle cells,miR-143-3p-3p,KLLN
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