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长链非编码 RNA SNHG12 在下肢深静脉血栓形成中的临床意义及作用机制。

Clinical significance and underlying mechanism of long non-coding RNA SNHG12 in lower extremity deep venous thrombosis.

机构信息

Department of Vascular Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.

Operating Room, The Affiliated Hospital of Qingdao University, Qingdao, China.

出版信息

Clin Transl Sci. 2024 Oct;17(10):e70023. doi: 10.1111/cts.70023.

DOI:10.1111/cts.70023
PMID:39396235
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11471149/
Abstract

D-dimer is widely used in the diagnosis of deep vein thrombosis (DVT), but the specificity is low. The study examined the diagnostic value of long non-coding RNA (lncRNA) SNHG12 in DVT, and preliminarily discussed its mechanism. SNHG12 levels were detected in 200 elderly fracture patients via RT-qPCR, including 38 DVTs. Logistic regression analysis and receiver operating characteristic (ROC) curve were applied for diagnostic value evaluation. HUVECs were used for function study. Cell proliferation, migration, apoptosis, release of inflammatory cytokines, and adhesion factors were detected. Student's t test and one-way ANOVA were applied for data comparison between two or among three or more groups. Correlation analysis of indicators was completed via Pearson's correlation analysis. Bioinformatics analysis predicted the target miRNAs and genes of SNHG12, with GO and KEGG for the function enrichment. It was found that SNHG12 was at low expression in DVT patients, and negatively correlated with D-dimer concentration (r = -0.535). SNHG12 and D-dimer were independent influence factors related to the development of DVT. SNHG12 and D-dimer combination had the best performance in DVT diagnosis. In HUVECs, SNHG12 promoted cell proliferation and migration and restricted the release of inflammatory cytokines and adhesion factors, but these influences were counteracted by miR-424-5p. A total of 208 overlapping target genes of miR-424-5p were identified, and their function was enriched in cellular cycle and senescence. PI3K-Akt signaling pathway was the most significant pathway based on KEGG results. In conclusion, SNHG12 had good diagnostic potential for DVT combined with D-dimer. SNHG12 maintains vascular endothelial cell function by acting as a competitive endogenous RNA (ceRNA) for miR-424-5p.

摘要

D-二聚体广泛用于深静脉血栓形成(DVT)的诊断,但特异性低。本研究探讨了长链非编码 RNA(lncRNA) SNHG12 在 DVT 中的诊断价值,并初步探讨了其机制。通过 RT-qPCR 检测 200 例老年骨折患者(包括 38 例 DVT 患者)中 SNHG12 的水平。应用逻辑回归分析和受试者工作特征(ROC)曲线评估诊断价值。应用 HUVEC 进行功能研究。检测细胞增殖、迁移、凋亡、炎症细胞因子和黏附因子的释放。采用 Student's t 检验和单因素方差分析比较两组或三组以上数据的差异。采用 Pearson 相关分析完成指标相关性分析。生物信息学分析预测 SNHG12 的靶 miRNA 和基因,GO 和 KEGG 进行功能富集。结果发现,DVT 患者 SNHG12 表达水平较低,与 D-二聚体浓度呈负相关(r=-0.535)。SNHG12 和 D-二聚体是 DVT 发生的独立影响因素。SNHG12 和 D-二聚体联合诊断 DVT 效果最佳。在 HUVEC 中,SNHG12 促进细胞增殖和迁移,限制炎症细胞因子和黏附因子的释放,但这些影响被 miR-424-5p 拮抗。共鉴定出 miR-424-5p 的 208 个重叠靶基因,其功能富集于细胞周期和衰老。基于 KEGG 结果,PI3K-Akt 信号通路是最显著的通路。结论:SNHG12 与 D-二聚体联合对 DVT 具有良好的诊断潜力。SNHG12 通过作为 miR-424-5p 的竞争性内源性 RNA(ceRNA)发挥作用,维持血管内皮细胞功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3101/11471149/cdd45c4ca498/CTS-17-e70023-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3101/11471149/463e24dde49e/CTS-17-e70023-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3101/11471149/01b3d1e0d1a6/CTS-17-e70023-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3101/11471149/5001a7b5f873/CTS-17-e70023-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3101/11471149/2ebe0c133465/CTS-17-e70023-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3101/11471149/cdd45c4ca498/CTS-17-e70023-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3101/11471149/463e24dde49e/CTS-17-e70023-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3101/11471149/ded2af71111d/CTS-17-e70023-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3101/11471149/01b3d1e0d1a6/CTS-17-e70023-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3101/11471149/5001a7b5f873/CTS-17-e70023-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3101/11471149/2ebe0c133465/CTS-17-e70023-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3101/11471149/cdd45c4ca498/CTS-17-e70023-g005.jpg

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