# LncRNA GAS6-AS2 regulates vascular smooth muscle cell senescence through the miR-138-5p/AKT1 axis and serves as a diagnostic and prognostic marker for atherosclerosis

## TL;DR

This study finds that the lncRNA GAS6-AS2 contributes to atherosclerosis by promoting vascular smooth muscle cell aging and inflammation, and could serve as a diagnostic and prognostic marker.

## Contribution

The study identifies GAS6-AS2 as a novel biomarker and regulatory axis (GAS6-AS2/miR-138-5p/AKT1) in atherosclerosis.

## Key findings

- GAS6-AS2 is upregulated in atherosclerosis patients and promotes vascular smooth muscle cell senescence.
- GAS6-AS2 regulates miR-138-5p and AKT1 to mediate inflammation and cell aging in atherosclerosis.
- GAS6-AS2 shows diagnostic and prognostic potential for atherosclerosis.

## Abstract

Atherosclerosis (AS) is a leading cause of cardiovascular-related death worldwide. The role and regulatory mechanism of GAS6-AS2 in AS remain unclear.

To investigate the diagnostic/prognostic value of GAS6-AS2 in AS and clarify its molecular mechanism.

107 AS patients and 105 healthy controls were included. The levels of GAS6-AS2, miR-138-5p, and mRNA were measured using RT-qPCR. ROC curve, K-M survival analysis, and Cox regression were performed to evaluate the diagnostic and prognostic value of GAS6-AS2. Bioinformatics prediction and dual-luciferase reporter assay were performed to verify the regulatory axis. Ox-LDL-induced VSMCs were used to construct an AS cell model. The biological functions were assessed using CCK-8, SA-β-Gal, and ELISA.

GAS6-AS2 expression was significantly increased in AS patients and in VSMCs treated with ox-LDL, and it showed high diagnostic accuracy and risk prediction for patients with AS. Knockdown of GAS6-AS2 reduced SA-β-Gal-positive cells, downregulated the expression of senescence-related genes and proteins (p16, p21, p53), and decreased the levels of inflammatory factors (IL-6, IL-1β) in ox-LDL-induced VSMCs. Mechanistically, GAS6-AS2 directly bound to miR-138-5p and inhibited its expression, while miR-138-5p targeted AKT1 to suppress its expression. Rescue experiments confirmed that the GAS6-AS2/miR-138-5p/AKT1 axis mediated ox-LDL-induced VSMC senescence and inflammation.

GAS6-AS2 is a potential diagnostic and prognostic biomarker for AS. It regulates ox-LDL-induced VSMC senescence and inflammatory response through the sponging of miR-138-5p to upregulate AKT1, providing a novel molecular target for AS treatment.

The online version contains supplementary material available at 10.1186/s41065-026-00650-5.