lncRNA PCA3 Suppressed Carotid Artery Stenosis and Vascular Smooth Muscle Cell Function via Negatively Modulating the miR-124-3p/ITGB1 Axis

Clin Appl Thromb Hemost. 2023 Jan-Dec:29:10760296231190383. doi: 10.1177/10760296231190383.

Abstract

Background & objectives: Due to the hidden pathogen, carotid artery stenosis (CAS) always occurred at an advanced stage leading to serious sequelae and even deaths. The significance of long noncoding RNA (lncRNA) prostate cancer antigen 3 (PCA3) in CAS incidence and progression were evaluated aiming to explore a potential target for its therapy.

Materials and methods: Serum samples were collected from 83 asymptomatic CAS patients and 52 healthy individuals and PCA3 was compared using polymerase chain reaction (PCR). The PCA3 levels were compared between stable and unstable plaque in CAS patients. The effect of PCA3 on vascular smooth muscle cells (VSMCs) proliferation and motility was assessed by CCK8 and transwell assay.

Results: PCA3 was downregulated in CAS patients and their unstable plaque tissues compared with healthy individuals and stable plaque, respectively. Reduced PCA3 could discriminate CAS patients with relatively high sensitivity and specificity and were associated with higher total cholesterol level and stenosis degree, unstable plaque, and complications. PCA3 downregulation predicted the adverse outcomes of CAS patients. In VSMCs, overexpressing PCA3 significantly suppressed cell proliferation, migration, and invasion, which was alleviated by miR-124-3p/ITGB1 axis.

Conclusion: PCA3 served as a biomarker of CAS and regulates the function of VSMCs through sponging miR-124-3p/ITGB1 and indirectly influence the stability of plaque.

Keywords: atherosclerosis; ceRNA; plaque stability; vascular smooth muscle cell.

MeSH terms

  • Carotid Stenosis* / genetics
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Humans
  • Male
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Muscle, Smooth, Vascular / metabolism
  • Plaque, Atherosclerotic*
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • RNA, Long Noncoding* / pharmacology

Substances

  • RNA, Long Noncoding
  • MicroRNAs
  • MIRN124 microRNA, human