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Knockdown of LINC00657 inhibits ox-LDL-induced endothelial cell injury by regulating miR-30c-5p/Wnt7b/β-catenin

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Abstract

Long noncoding RNAs (lncRNAs) play pivotal roles in the pathogenesis, development, and treatment of atherosclerosis (AS). The endothelial cell injury is a feature of AS. However, the role and mechanism of lncRNA LINC00657 in oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell injury remain unclear. The serum samples were collected from 32 AS patients and normal volunteers. Ox-LDL-treated human umbilical vein endothelial cells (HUVEC) were used for the experiments in vitro. The levels of LINC00657, microRNA (miR)-30c-5p and Wnt family member 7B (Wnt7b) were measured by quantitative real-time polymerase chain reaction or western blot. The expression levels of proteins in Wnt7b/β-catenin pathway or endothelial-mesenchymal transition (EndMT) were detected by western blot. The secretion of inflammatory cytokine was examined by enzyme linked immunosorbent assay (ELISA). Cell viability and apoptosis were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide, flow cytometry, and western blot. The target association of miR-30c-5p and LINC00657/Wnt7b was analyzed via dual-luciferase reporter assay and RNA pull-down assay. LINC00657 expression was increased in AS serum and ox-LDL-treated HUVEC cells. LINC00657 knockdown suppressed ox-LDL-induced Wnt7b/β-catenin activation, EndMT, inflammatory response, and apoptosis in HUVEC cells. MiR-30c-5p was bound to LINC00657 and it knockdown reversed the role of LINC00657 inhibition in ox-LDL-induced HUVEC cell injury. MiR-30c-5p targeted Wnt7b to inhibit ox-LDL-induced Wnt7b/β-catenin activation, EndMT, inflammatory response, and apoptosis in HUVEC cells. Silence of LINC00657 repressed ox-LDL-induced injury via inhibiting EndMT, inflammatory response, and apoptosis in HUVEC cells by regulating miR-30c-5p/Wnt7b/β-catenin, indicating a potential target for treatment of AS.

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  1. Haojie Wu and Tingting Liu were contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, Xi’an No. 1 Hospital, Xi’an, Shaanxi, China

    Haojie Wu

  2. Department of Respiratory Medicine, The Second Medical Center of PLA General Hospital, Beijing, China

    Tingting Liu

  3. Department of Cardiology, Xi’an No. 3 Hospital, No. 10, East Section of Fengcheng Third Road, Weiyang District, Xi’an, 710000, Shaanxi, China

    Hong Hou

  4. Department of Cardiology, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277, West Yanta Road, Xi’an, 710000, Shaanxi, China

    Hong Hou

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  1. Haojie Wu
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Wu, H., Liu, T. & Hou, H. Knockdown of LINC00657 inhibits ox-LDL-induced endothelial cell injury by regulating miR-30c-5p/Wnt7b/β-catenin. Mol Cell Biochem 472, 145–155 (2020). https://doi.org/10.1007/s11010-020-03793-9

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