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GAS5 knockdown suppresses inflammation and oxidative stress induced by oxidized low-density lipoprotein in macrophages by sponging miR-135a

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Abstract

A large number of long non-coding RNAs have been confirmed to play vital roles in regulating various biological processes. Abnormal expression of growth arrest-specific transcript 5 (GAS5) is reported to be involved in the development of atherosclerosis (AS). This work is to explore the detailed mechanism underling how GAS5 regulates AS progression. We found that the abundance of GAS5 was markedly increased, and miR-135a was decreased in AS patient serums and ox-LDL-induced human THP-1 cells dose and time dependently. Interference of GAS5 suppressed inflammation and oxidative stress induced by ox-LDL in THP-1 cells. Mechanistically, GAS5 acted as a molecular sponge of microRNA-135a (miR-135a). Rescue assays indicated that knockdown of miR-135a partially rescued small interference RNA for GAS5-inhibited inflammatory cytokines release and oxidative stress in ox-LDL-triggered THP-1 cells. In conclusion, the absence of GAS5-inhibited inflammatory response and oxidative stress induced by ox-LDL in THP-1 cells via sponging miR-135a, providing a deep insight into the molecular target for AS treatment.

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Authors and Affiliations

  1. Department of Pathology, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, No.150, Old Town Street, Linhai, Zhejiang, China

    Yunyan Zhang, Xianben Lu, Minjun Yang, Jiaolin Shangguan & Yanping Yin

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  1. Yunyan Zhang
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Correspondence to Yanping Yin.

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The present study was performed with the approval of the Research Ethics Committee of Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, and all participants signed the written informed consent prior to this study.

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11010_2020_3962_MOESM1_ESM.tif

Supplementary file1 The correlation analysis between GAS5 and inflammatory factors in AS patients. (A-C) Inflammatory cytokines IL-1β, IL-6, and TNF-α in serums samples from AS patients (n=26) and healthy donors (n=18) was detected. (D-F) Pearson correlation analysis was applied to evaluate the expression association between GAS5 and Inflammatory cytokines IL-1β, IL-6, and TNF-α in AS patients. GAS5= growth-arrest specific transcript 5, I = interleukin, TNF = tumor necrosis factor. *P < 0.05 (TIF 929 kb)

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Zhang, Y., Lu, X., Yang, M. et al. GAS5 knockdown suppresses inflammation and oxidative stress induced by oxidized low-density lipoprotein in macrophages by sponging miR-135a. Mol Cell Biochem 476, 949–957 (2021). https://doi.org/10.1007/s11010-020-03962-w

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