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LncRNA XIST knockdown ameliorates oxidative low-density lipoprotein-induced endothelial cells injury by targeting miR-204-5p/TLR4

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Abstract

Oxidative low-density lipoprotein (ox-LDL)-induced endothelial cell injury is a key contributor to atherosclerosis development. However, the role and mechanism of long noncoding RNA X-inactive specific transcript (XIST) in atherosclerosis remain largely unknown. The ox-LDL-induced human umbilical vein endothelial cells (HUVECs) injury was analyzed by cell viability, apoptosis, inflammatory cytokines secretion and oxidative stress. The expression levels of XIST, microRNA-204-5p (miR-204-5p) and toll-like receptor 4 (TLR4) were detected by quantitative real-time polymerase chain reaction and western blot, respectively. The target interaction between miR-204-5p and XIST or TLR4 was explored by bioinformatics analysis, luciferase assay and RNA immunoprecipitation. The expression of XIST was enhanced in ox-LDL-treated HUVECs. Knockdown of XIST attenuated ox-LDL-induced viability inhibition, apoptosis production, inflammatory response and oxidative stress in HUVECs. XIST was validated as a sponge of miR-204-5p and TLR4 acted as a target of miR-204-5p. Knockdown of miR-204-5p reversed silence of XIST-mediated suppressive role in ox-LDL-induced injury. TLR4 alleviated miR-204-5p-mediated inhibitive effect on ox-LDL-induced injury. Moreover, XIST could regulate TLR4 expression by sponging miR-204-5p. In conclusion, silence of XIST displayed a protective role in ox-LDL-induced injury in HUVECs by regulating miR-204-5p/TLR4 axis, providing a novel mechanism for understanding the pathogenesis of atherosclerosis.

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Figure 5: TLR4 is a target of miR-204-5p.
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Abbreviations

ELISA:

enzyme-linked immunosorbent assay

HUVECs:

human umbilical vein endothelial cells

lncRNAs:

long noncoding RNAs

ox-LDL:

oxidative low-density lipoprotein

qRT-PCR:

quantitative real-time polymerase chain reaction

RIP:

RNA immunoprecipitation

TLR4:

toll-like receptor 4

XIST:

X-inactive specific transcript

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Authors and Affiliations

  1. Department of Vascular Surgery, The Huaian Hospital Affiliated to Xuzhou Medical University, Huai’an, Jiangsu, China

    Guoyong Lu, Peng Tian, Yongxin Zhu & Xiaohua Zuo

  2. Department of Vascular Surgery, The Second People’s Hospital of Huai’an, Huai’an, Jiangsu, China

    Guoyong Lu, Peng Tian, Yongxin Zhu & Xiaohua Zuo

  3. Department of Vascular Surgery, Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, Jiangsu, China

    Xiaoqiang Li

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  1. Guoyong Lu
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  2. Peng Tian
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  3. Yongxin Zhu
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  4. Xiaohua Zuo
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  5. Xiaoqiang Li
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Correspondence to Xiaoqiang Li.

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Communicated by Ullas Kolthur-Seetharam.

Corresponding editor: Ullas Kolthur-Seetharam

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Lu, G., Tian, P., Zhu, Y. et al. LncRNA XIST knockdown ameliorates oxidative low-density lipoprotein-induced endothelial cells injury by targeting miR-204-5p/TLR4. J Biosci 45, 52 (2020). https://doi.org/10.1007/s12038-020-0022-0

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