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Circular RNA circUBR4 regulates ox-LDL-induced proliferation and migration of vascular smooth muscle cells through miR-185-5p/FRS2 axis

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Abstract

Circular RNAs (circRNAs) have been reported to play vital roles in atherosclerosis. However, the precise roles of circUBR4 in atherosclerosis remain unclear. The purpose of this study is to investigate the regulatory roles of circUBR4 in atherosclerosis. The expression levels of circUBR4, miR-185-5p, and Fibroblast growth factor receptor substrate 2 (FRS2) were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR) assay. Human vascular smooth muscle cells (VSMCs) were treated with oxidized low-density lipoprotein (ox-LDL) to mimic atherosclerosis condition in vitro. Cell proliferation was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT), colony-forming, and 5-ethynyl-2′-deoxyuridine (EdU) assays. Wound healing and transwell assays were used to assess cell migration. The interaction relationship between miR-185-5p and circUBR4 or FRS2 was confirmed by dual-luciferase reporter and RNA pull-down assays. CircUBR4 was overexpressed in atherosclerosis patients and VSMCs treated with ox-LDL, and the knockdown of circUBR4 abolished ox-LDL-induced enhanced effects on the proliferation and migration of VSMCs. MiR-185-5p, interacted with FRS2, was a target of circUBR4 in VSMCs. The silencing of miR-185-5p reversed the effects caused by circUBR4 knockdown on ox-LDL-induced VSMCs. In addition, overexpression of miR-185-5p suppressed the proliferation and migration of VSMCs by targeting FRS2. CircUBR4 contributed to ox-LDL-induced VSMC proliferation and migration through up-regulating FRS2 via miR-185-5p.

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Funding

This work was supported by Scientific research project approved by Heilongjiang Provincial Health Committee in 2019 (No. 2019-253).

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Author notes

  1. Chen Sun, Jinliang Li and Ying Li contributed equally to this paper.

Authors and Affiliations

  1. Department of Internal Medicine, Yantai Municipal Government Hospital, Yantai, Shandong, China

    Chen Sun

  2. Department of Cardiology, Harbin Sixth Hospital, Harbin, Heilongjiang, China

    Jinliang Li

  3. Department of Emergency, First Teaching Hospital of Tianjin University of TCM, Tianjin, China

    Ying Li

  4. Department of Disinfection and Vector Control, Yantai Center for Disease Prevention and Control, Yantai, Shandong, China

    Li Li

  5. Department of Cardiovascular Medicine, Chongqing Dazu District People’s Hospital, No. 1073 Erhuan South Road, Tangxiang Street, Dazu County, Chongqing, 402360, China

    Guopeng Huang

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  1. Chen Sun
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  3. Ying Li
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  4. Li Li
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Contributions

CS, JL and YL were responsible for the conception and design of the research. CS, YL and LL performed the experiments. CS, JL and GH interpreted the results of the experiments. CS analysed the data, prepared the figures, and drafted the manuscript. JL, YL, LL, and GH edited and revised the manuscript. All authors approved the final version of the report.

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Correspondence to Guopeng Huang.

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Written informed consent was obtained from patients with approval by the Institutional Review Board in Yantai City Municipal Government Hospital.

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Sun, C., Li, J., Li, Y. et al. Circular RNA circUBR4 regulates ox-LDL-induced proliferation and migration of vascular smooth muscle cells through miR-185-5p/FRS2 axis. Mol Cell Biochem 476, 3899–3910 (2021). https://doi.org/10.1007/s11010-021-04207-0

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