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MiR-140-5p inhibits oxidized low-density lipoprotein-induced oxidative stress and cell apoptosis via targeting toll-like receptor 4

Gene Therapy volume 28, pages 413–421 (2021)Cite this article

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Abstract

Critical roles of several microRNAs have been implicated in atherosclerosis (AS). In this study, we studied the functional role of miR-140-5p in AS. An AS model was constructed in THP-1 macrophages challenged with oxidized low-density lipoprotein (ox-LDL). The expression of miR-140-5p was up- or downregulated with corresponding mimic or inhibitor regents. Our experiments showed that the levels of cell apoptosis and fatty acid accumulation were decreased in THP-1 macrophages treated with miR-140-5p mimic, whereas increased in those treated with miR-140-5p inhibitor. The levels of ROS (reactive oxygen species), MDA (malondialdehyde), TC (Triglyceride), and TG (total cholesterol) were reduced and the level of SOD (superoxide dismutase) was improved in miR-140-5p overexpressed THP-1 macrophages, which can be reversed with miR-140-5p depletion. Moreover, through bioinformatics analysis, we found toll-like receptor 4 (TLR4) was a potential target of miR-140-5p. Luciferase reporter assay demonstrated that miR-140-5p regulated TLR4 expression via binding 3′UTR of TLR4 in THP-1 macrophages. In ox-LDL challenged THP-1 macrophages, the expression of TLR4 was decreased after miR-140-5p mimic transfection, whereas improved after treatment with miR-140-5p inhibitors. As a conclusion, miR-140-5p can participate in inhibiting ox-LDL-induced oxidative stress and cell apoptosis via targeting TLR4 in macrophage-mediated ox-LDL induced AS.

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Fig. 1: The cell apoptosis and miR-140-5p expression in THP-1 macrophages after challenging with ox-LDL.
Fig. 2: Influence of miR-140-5p on the development of ox-LDL-induced macrophages derived foam cells.
Fig. 3: Effect of miR-140-5p on oxidative stress and apoptosis caused by ox-LDL in THP-1 macrophages.
Fig. 4: The proliferation of HUVSMC cells; TLR4 as a target of miR-140-5p.
Fig. 5: In AS, miR-140-5p expression was downregulated.

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Data availability

The data sets used in this study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the Outstanding Youth Training Project from Shanghai Ninth People’s Hospital [Grant No. jyyq 08201607], the National Natural Science Foundation of China [Grant Nos. 81400802 and 81670735], and Clinical Research Project of Multi-Disciplinary Team, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine [Grant No. 201701022].

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  1. These authors contributed equally: Huifang Liu, Ziming Mao

Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Huifang Liu, Ziming Mao, Jing Zhu, Minyan Shen & Fengling Chen

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  1. Huifang Liu
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  2. Ziming Mao
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Contributions

FC designed and supervised the study; HL, ZM, JZ and MS performed the experiments; HL and ZM collected and analyzed the data; JZ and MS supported administration, technique, and materials; HL prepared the paper; FC revised the paper; All authors read and approved the final paper.

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Correspondence to Fengling Chen.

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Liu, H., Mao, Z., Zhu, J. et al. MiR-140-5p inhibits oxidized low-density lipoprotein-induced oxidative stress and cell apoptosis via targeting toll-like receptor 4. Gene Ther 28, 413–421 (2021). https://doi.org/10.1038/s41434-020-0139-7

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