Clinical significance of lncRNA GAS5 in deep vein thrombosis and its mechanism of action on vascular endothelial damage

The current research aims to clarify the clinical significance and molecular function of long-non-coding RNA growth arrest-specific 5 (GAS5) in deep vein thrombosis (DVT). 92 DVT patients and 86 controls were included in this study. Real-time quantitative reverse transcription PCR (RT-qPCR) was performed to measure GAS5, microRNA (miR)-134-5p, and forkhead box protein 3 (FOXP3) levels. Receiver operating characteristic (ROC) curves evaluated the diagnostic significance of GAS5 in DVT. Kaplan-Meier and Cox regression analyses assessed the prognostic significance of post-thrombotic syndrome (PTS). An in vitro model using CoCl 2 -induced HUVECs was established to measure cell proliferation, apoptosis, adhesion factors, and inflammatory factors via Cell Counting Kit-8 (CCK-8), flow cytometry, RT-qPCR, and Enzyme-linked immunosorbent assay (ELISA). Protein expression of FOXP3, HIF-1α, and VEGFA was evaluated via Western blot. Dual luciferase report, RIP, and RNA pull-down assays confirmed the direct binding of miR-134-5p to GAS5 or FOXP3. GAS5 and FOXP3 were downregulated in DVT patients’ serum and CoCl 2 -induced HUVECs, while miR-134-5p was upregulated. GAS5 distinguished DVT patients from controls with 89.13% sensitivity and 83.72% specificity. At 18-month follow-up, 32.60% of patients developed PTS, which was more common among those with low GAS5 expression. Mechanistically, GAS5 and FOXP3 bind to miR-134-5p. CoCl 2 enhanced the protein levels of HIF-1α and VEGFA. Higher GAS5 levels reduced CoCl 2 -induced proliferation suppression, apoptosis promotion, and adhesion and inflammatory factors upregulation in HUVECs, but miR-134-5p reversed this effect. GAS5 levels are decreased in DVT patients, serving as a diagnostic and prognostic biomarker. Elevated GAS5 targets miR-134-5p/FOXP3 axis to alleviate endothelial dysfunction and inflammation, thereby reducing thrombosis.