Linc00657 promoted pyroptosis in THP-1-derived macrophages and exacerbated atherosclerosis via the miR-106b-5p/TXNIP/NLRP3 axis

Long intergenic non-coding RNA 00657 (linc00657) is involved in various diseases, whereas its role in atherosclerosis (AS) development remains inconclusive. This study was designed to investigate the effects and underlying mechanisms of linc00657 in atherogenesis. The results showed that ox-LDL trea...

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Bibliographic Details
Published in:International journal of biological macromolecules 2023-12, Vol.253, p.126953-126953, Article 126953
Main Authors: Liang, Yin, Xu, Xiao-Dan, Xu, Xi, Cai, Yang-Bo, Zhu, Zi-Xian, Zhu, Lin, Ren, Kun
Format: Article
Language:English
Subjects:
Atherosclerosis
linc00657
Pyroptosis
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Summary:Long intergenic non-coding RNA 00657 (linc00657) is involved in various diseases, whereas its role in atherosclerosis (AS) development remains inconclusive. This study was designed to investigate the effects and underlying mechanisms of linc00657 in atherogenesis. The results showed that ox-LDL treatment significantly induced pyroptosis in human THP-1-derived macrophages. The secretion levels of LDH and pro-inflammatory factors were markedly enhanced, and the integrity of plasma membranes was disrupted in ox-LDL-treated THP-1-derived macrophages. These effects were significantly compensated after transfection with linc00657 siRNA and became more evident by linc00657 overexpression. Moreover, the effects of linc00657 overexpression on pyroptosis of THP-1-derived macrophages can also be robustly reversed by TXNIP knockdown or miR-106b-5p mimics transfection. Mechanistically, linc00657 enhanced TXNIP expression by competitively binding to miR-106b-5p, promoting NLRP3 inflammasome activation. Finally, we found that linc00657 overexpression significantly increased the expression of pyroptosis-related factors and decreased miR-106b-5p level in the aorta of high-fat-diet-fed apoE−/− mice. Furthermore, linc00657 up-regulation enlarged the plaque area, exacerbated plasma lipid profile, and increased pro-inflammatory cytokines levels in the serum, effects that were reversed by injection of miR-106b-5p agomir. This evidence indicated that linc00657 stimulated macrophage pyroptosis and aggravated the progression of AS via the miR-106b-5p/TXNIP/NLRP3 pathway.
ISSN:0141-8130
1879-0003
DOI:10.1016/j.ijbiomac.2023.126953