长链非编码RNA CASC2通过海绵吸附miR-152-3p介导下肢深静脉血栓形成。

LncRNA CASC2 mediates the lower extremity deep vein thrombosis via sponging miR-152-3p.

作者信息

Wang Shuping, Yang Hongyu, Wang Fei, Li Li

机构信息

Department of Clinical Laboratory, Affiliated Hospital of PanZhiHua University, No.27 Taoyuan Street, Bingcaogang, East District, Panzhihua City, 617000, Sichuan Province, China.

出版信息

J Thromb Thrombolysis. 2025 Jul 1. doi: 10.1007/s11239-025-03145-8.

DOI:10.1007/s11239-025-03145-8

PMID:40593456

Abstract

BACKGROUND

Lower extremity deep vein thrombosis (DVT) is a prevalent form of peripheral vascular disease, notable for its high incidence rate. We investigated the potential mechanisms through which the long non-coding RNA (lncRNA) CASC2/miR-152-3p axis regulates the DVT.

METHODS

150 patients diagnosed with DVT and 150 controls were included. CASC2 and miR-152-3p levels were quantified using RT-qPCR. HUVECs viability was assessed via the CCK-8 assay, while cell migration was evaluated using Transwell chamber assays. Flow cytometry was employed to determine cell apoptosis. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), ICAM, and VCAM concentrations were measured through ELISA. The interaction between lncRNA CASC2 and miR-152-3p was validated using a dual-luciferase reporter assay. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted for function and pathway enrichment.

RESULTS

LncRNA CASC2 was significantly downregulated in DVT patients. LncRNA CASC2 was independently associated with the occurrence of DVT and demonstrated a relatively high diagnostic value. Overexpression of lncRNA CASC2 significantly enhanced HUVEC's proliferation and migration, while reducing apoptosis and the concentrations of TNF-α, IL-1β, IL-6, ICAM-1, and VCAM-1. Conversely, the knockdown of lncRNA CASC2 resulted in opposite effects. LncRNA CASC2 directly targeted and negatively regulated miR-152-3p. Additionally, miR-152-3p counteracted the effects of lncRNA CASC2 on cell function. GO and KEGG analyses revealed that the target genes of miR-152-3p were mainly involved in the TGF-β and PI3K-Akt signaling pathways.

CONCLUSION

The lncRNA CASC2/miR-152-3p axis played a critical role in mediating the formation of DVT.

摘要

背景

下肢深静脉血栓形成（DVT）是外周血管疾病的一种常见形式，发病率很高。我们研究了长链非编码RNA（lncRNA）CASC2/miR-152-3p轴调节DVT的潜在机制。

方法

纳入150例诊断为DVT的患者和150例对照。使用RT-qPCR定量CASC2和miR-152-3p水平。通过CCK-8法评估人脐静脉内皮细胞（HUVECs）活力，同时使用Transwell小室试验评估细胞迁移。采用流式细胞术测定细胞凋亡。通过酶联免疫吸附测定（ELISA）测量肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、细胞间黏附分子（ICAM）和血管细胞黏附分子（VCAM）浓度。使用双荧光素酶报告基因试验验证lncRNA CASC2与miR-152-3p之间的相互作用。进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析以进行功能和通路富集。

结果

lncRNA CASC2在DVT患者中显著下调。lncRNA CASC2与DVT的发生独立相关，并显示出相对较高的诊断价值。lncRNA CASC2的过表达显著增强了HUVEC的增殖和迁移，同时减少了细胞凋亡以及TNF-α、IL-1β、IL-6、ICAM-1和VCAM-1的浓度。相反，lncRNA CASC2的敲低产生了相反的效果。lncRNA CASC2直接靶向并负调节miR-152-3p。此外，miR-152-3p抵消了lncRNA CASC2对细胞功能的影响。GO和KEGG分析显示，miR-152-3p的靶基因主要参与转化生长因子-β（TGF-β）和磷脂酰肌醇-3激酶-蛋白激酶B（PI3K-Akt）信号通路。