Scholarlink

Background <p>Atherosclerosis (AS) is a leading cause of cardiovascular-related death worldwide. The role and regulatory mechanism of GAS6-AS2 in AS remain unclear.</p> Aim <p>To investigate the diagnostic/prognostic value of GAS6-AS2 in AS and clarify its molecular mechanism.</p> Methods <p>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.</p> Results <p>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.</p> Conclusions <p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月4日

查看全文
  • Wei Dong,
  • Zhencheng Li,
  • Kai Xie,
  • Xiaowen Lai,
  • Zhaochuan Luo,
  • Yun Qiu,
  • Huan Pu,
  • Ying Zhang

摘要

Background

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

Aim

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

Methods

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.

Results

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.

Conclusions

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.