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LINC01088靶向miR-195-5p以促进增殖和迁移并减少细胞凋亡从而抑制颈动脉狭窄

LINC01088 Targets miR-195-5p to Promote Proliferation and Migration and Reduce Apoptosis in the Inhibition of Carotid Artery Stenosis.

作者信息

Tang Huoquan, Sun Shuo, Zhang Yali, Jin Ying, Wang Caijiao, Xu Chunchun, Zhang Yanfeng, Chen Li, Wu Defeng

机构信息

Department of Neurosurgery, Taiyuan Iron & Steel (Group) Co. General Hospital, Taiyuan, China.

Department of Neurosurgery, The Affiliated Hospital of Hebei University, Baoding, China.

出版信息

Clin Appl Thromb Hemost. 2025 Jan-Dec;31:10760296251319281. doi: 10.1177/10760296251319281. Epub 2025 Mar 25.

DOI:10.1177/10760296251319281
PMID:40129392
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11946290/
Abstract

Carotid artery stenosis (CAS) often goes undetected until it reaches an advanced stage, which can result in serious complications. The present study evaluated the potential of long noncoding RNA (lncRNA) LINC01088 as a biomarker for CAS. 92 CAS patients and 92 healthy controls (Control group) were included. RT-qPCR was performed to assess the relative levels of LINC01088 and miR-195-5p. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic potential of LINC01088. The relationship between LINC01088 and miR-195-5p was identified by luciferase reporter assay. Proliferation, migration, and apoptosis in human aortic endothelial cells (HAECs) were assessed using CCK8, transwell, and flow cytometry assay. DAVID was employed for Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. CAS patients showed decreased LINC01088 expression and increased miR-195-5p expression compared to Control, with a negative correlation between their expression levels in CAS. LINC01088 demonstrated high sensitivity and specificity in distinguishing CAS patients from healthy individuals. LINC01088 directly targets miR-195-5p. Upregulation of LINC01088 reversed the effects of ox-LDL treatment, restoring proliferation and migration while reducing apoptosis in HAECs. However, miR-195-5p mimic reduced the protection of LINC01088 on HAECs proliferation, migration, and apoptosis. For miR-195-5p target genes, GO revealed protein metabolism pathways and KEGG highlighted the p53 and MAPK signaling pathways. The present study revealed the diagnosis value of LINC01088. LINC01088 reversed ox-LDL-induced proliferation, apoptosis, and migration by acting as sponges of miR-195-5p in HAECs. LINC01088 may serve as a protective biomarker in CAS progression.

摘要

颈动脉狭窄(CAS)通常在发展到晚期之前都未被发现,这可能会导致严重的并发症。本研究评估了长链非编码RNA(lncRNA)LINC01088作为CAS生物标志物的潜力。纳入了92例CAS患者和92例健康对照者(对照组)。采用逆转录定量聚合酶链反应(RT-qPCR)来评估LINC01088和miR-195-5p的相对水平。使用受试者工作特征(ROC)曲线来评估LINC01088的诊断潜力。通过荧光素酶报告基因检测确定LINC01088与miR-195-5p之间的关系。使用细胞计数试剂盒-8(CCK8)、Transwell小室和流式细胞术检测评估人主动脉内皮细胞(HAECs)的增殖、迁移和凋亡。利用DAVID进行京都基因与基因组百科全书(KEGG)和基因本体论(GO)分析。与对照组相比,CAS患者的LINC01088表达降低,miR-195-5p表达升高,且在CAS患者中它们的表达水平呈负相关。LINC01088在区分CAS患者和健康个体方面表现出高灵敏度和特异性。LINC01088直接靶向miR-195-5p。LINC01088的上调逆转了氧化型低密度脂蛋白(ox-LDL)处理的影响,恢复了HAECs的增殖和迁移,同时减少了细胞凋亡。然而,miR-195-5p模拟物降低了LINC01088对HAECs增殖、迁移和凋亡的保护作用。对于miR-195-5p的靶基因,GO分析显示蛋白质代谢途径,KEGG分析突出了p53和丝裂原活化蛋白激酶(MAPK)信号通路。本研究揭示了LINC01088的诊断价值。LINC01088通过作为HAECs中miR-195-5p的海绵,逆转了ox-LDL诱导的增殖、凋亡和迁移。LINC01088可能作为CAS进展中的一种保护性生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b40/11946290/232744065d6b/10.1177_10760296251319281-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b40/11946290/fee45c49037e/10.1177_10760296251319281-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b40/11946290/93f0216aaf4a/10.1177_10760296251319281-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b40/11946290/0d0422e1bd97/10.1177_10760296251319281-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b40/11946290/232744065d6b/10.1177_10760296251319281-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b40/11946290/fee45c49037e/10.1177_10760296251319281-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b40/11946290/93f0216aaf4a/10.1177_10760296251319281-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b40/11946290/0d0422e1bd97/10.1177_10760296251319281-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b40/11946290/232744065d6b/10.1177_10760296251319281-fig4.jpg

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