Abstract
Atherosclerosis (AS) is the main cause of cardiovascular diseases. However, the role of AQP9 in AS is not well understood. In the present study, we predicted that miR-330-3p might regulate AQP9 in AS through bioinformatics analysis, and we established AS model using ApoE−/− mouse (C57BL/6) with high-fat diet (HFD). Hematoxylin and eosin (H&E) and Oil red O staining were used to determine atherosclerotic lesions. CCK8 and Ethyny1-2-deoxyuridine (EdU) assays were used to investigate human umbilical vein endothelial cells (HUVECs) proliferation after treatment with 100 μg/mL ox-LDL. Wound scratch healing and transwell assays were used to measure the cell invasion and migration ability. Flow cytometry assay was used to determine apoptosis and cell cycle. A dual-luciferase reporter assay was performed to investigate the binding of miR-330-3p and AQP9. We identified that the expression of miR-330-3p in AS mice model decreased while the expression level of AQP9 increased. miR-330-3p overexpression or down-regulation of AQP9 could reduce cell apoptosis, promote cell proliferation, and migration after ox-LDL treatment. Dual-luciferase reporter assay result presented that AQP9 was directly inhibited by miR-330-3p. These results suggest that miR-330-3p inhibits AS by regulating AQP9. miR-330-3p/AQP9 axis may be a new therapeutic target for AS.
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The dataset used and/or analyzed in this study is available from the corresponding author on reasonable request.
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This study was supported by the Scientific Research Project of collages and universities in Anhui Province (2022AH051514).
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YG contributed to the conception and design. ES carried out the experiment and wrote the paper. YY, WT, WW, and XW analyzed the data and discusses the result. ES, SZ, and YG revised the manuscript.
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Approval to obtain experimental tissues from patients with atherosclerosis and normal controls was obtained under informed consent. This study was reviewed and approved by the Ethic Committee of the first clinical college of Jinan University (2020173).
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The study was performed in accordance with the ethical standards as laid down in the Regulations on the Management of Laboratory Animals of China and approved by the ethics committee of the first clinical college of Jinan University.
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Shan, E., Yu, Y., Tang, W. et al. miR-330-3p alleviates the progression of atherosclerosis by downregulating AQP9. Funct Integr Genomics 23, 77 (2023). https://doi.org/10.1007/s10142-023-01001-7
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DOI: https://doi.org/10.1007/s10142-023-01001-7