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长链非编码RNA SCARNA8通过抑制巨噬细胞胞葬作用促进动脉粥样硬化斑块不稳定。

LncRNA SCARNA8 promotes atherosclerotic plaque instability by inhibiting macrophage efferocytosis.

作者信息

Yin Xiaoliang, Chen Xiaodong, Wang Tao, Yang Jianling, Yu Jiahui, Yang Jun

机构信息

Department of Neurosurgery, Peking University Third Hospital, Beijing, China.

Center for Precision Neurosurgery and Oncology, Peking University Health Science Center, Beijing, China.

出版信息

Epigenetics. 2025 Dec;20(1):2487317. doi: 10.1080/15592294.2025.2487317. Epub 2025 May 13.

Abstract

In recent years, findings suggest that long noncoding RNAs (lncRNAs) are closely related to the development of atherosclerosis (AS), but there is a lack of studies on the involvement of lncRNA-regulated cytosolic burial in the regulation of AS. In this study, we investigated the mechanism by which lncRNA SCARNA8 affects macrophage cell burial to regulate AS. The cytosolic burial-associated target gene regulated by lncRNA SCARNA8 was PPARG. LncRNA SCARNA8 was increased in the carotid unstable plaque group, whereas PPARG was decreased. Ox-LDL led to the up-regulation of lncRNA SCARNA8 expression and apoptosis in Raw264.7 cells in a time-, concentration-dependent manner. Knockdown of lncRNA SCARNA8 upregulated PPARG and reduced apoptosis in Raw264.7 cells. In addition, knockdown of lncRNA SCARNA8 improved the stability of atherosclerotic plaques by promoting cellular burial of Raw264.7 cells. LncRNA SCARNA8 is a key regulator of plaque vulnerability, and targeting lncRNA SCARNA8 May provide a novel means for the prevention and treatment of AS.

摘要

近年来,研究结果表明长链非编码RNA(lncRNAs)与动脉粥样硬化(AS)的发生发展密切相关,但关于lncRNA调控的胞葬作用参与AS调节的研究尚少。在本研究中,我们探究了lncRNA SCARNA8影响巨噬细胞胞葬作用以调节AS的机制。由lncRNA SCARNA8调控的与胞葬作用相关的靶基因是PPARG。在颈动脉不稳定斑块组中,lncRNA SCARNA8升高,而PPARG降低。氧化型低密度脂蛋白(Ox-LDL)以时间和浓度依赖性方式导致Raw264.7细胞中lncRNA SCARNA8表达上调和细胞凋亡。敲低lncRNA SCARNA8可上调Raw264.7细胞中的PPARG并减少细胞凋亡。此外,敲低lncRNA SCARNA8通过促进Raw264.7细胞的胞葬作用提高了动脉粥样硬化斑块的稳定性。LncRNA SCARNA8是斑块易损性的关键调节因子,靶向lncRNA SCARNA8可能为AS的防治提供新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5d4/12077458/ec086c078a58/KEPI_A_2487317_F0001_OC.jpg

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