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LincRNA-p21 alleviates atherosclerosis progression through regulating the miR-221/SIRT1/Pcsk9 axis |
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| Authors: | Haojie Wang Fei He Bing Liang Yuanhu Jing Pei Zhang Weichao Liu Bowen Zhu Dongmei Dou |
| Affiliation: | 1. Thoracic & Cardiovascular Surgery, Huaihe Hospital of Henan University, Kaifeng, China Contribution: Conceptualization (supporting), Writing - original draft (supporting), Writing - review & editing (supporting);2. Thoracic & Cardiovascular Surgery, Huaihe Hospital of Henan University, Kaifeng, China Contribution: Data curation (supporting), Formal analysis (supporting), Funding acquisition (supporting), Writing - original draft (supporting), Writing - review & editing (supporting);3. Thoracic & Cardiovascular Surgery, Huaihe Hospital of Henan University, Kaifeng, China Contribution: Investigation (supporting), Writing - original draft (supporting), Writing - review & editing (supporting);4. School of Clinical Medicine, Henan University, Kaifeng, China Contribution: Conceptualization (supporting), Writing - original draft (supporting), Writing - review & editing (supporting);5. Institute of Chronic Disease Risks Assessment, Henan University, Kaifeng, China |
| Abstract: | Atherosclerosis (AS) is the main aetiology of coronary heart disease, cerebral infarction and peripheral vascular disease in humans. Long-noncoding RNA (LincRNA)-p21 has been reported to participate in the development of AS. Therefore, this study was designed to investigate the mechanism of LincRNA-p21 on suppressing the development of AS. We fed ApoE−/− mice with a high-fat diet to induce an AS mouse model where the lesion area of AS and the extent of lipid deposition were measured. The binding of LincRNA-p21 and miR-221 or miR-221 and SIRT1 was measured using a dual luciferase reporter gene assay and RIP. Following loss- and gain- function assays, CCK8, EdU, Transwell assay and scratch test were performed to determine the biological processes of human aortic endothelial cells (HAECs). miR-221 was highly expressed while SIRT1 was poorly expressed in AS. LincRNA-p21 acted as a sponge for miR-221. miR-221 targeted and negatively regulated the expression of SIRT1. LincRNA-p21 promoted the deacetylation of Pcsk9 by SIRT1 by competitively binding to miR-221, whereby promoting HAEC proliferation, migration and tube formation. In conclusion, LincRNA-p21 acted as a molecular sponge for miR-221 to promote deacetylation of the promoter region of Pcsk9 by SIRT1, therefore preventing the development of AS. |
| Keywords: | atherosclerosis long intergenic noncoding RNA-p21 microRNA-221 proprotein convertase subtilisin/kexin type 9 sirtuin 1 |