Hsa_circ_0029589 knockdown inhibits the proliferation, migration and invasion of vascular smooth muscle cells via regulating miR-214-3p and STIM1

Life Sci. 2020 Oct 15:259:118251. doi: 10.1016/j.lfs.2020.118251. Epub 2020 Aug 11.

Abstract

Aims: Circular RNAs (circRNAs) are relevant to atherosclerosis progression. However, the role and mechanism of circRNA hsa_circ_0029589 (circ_0029589) in atherosclerosis are not fully understood. This research aims to explore the function and mechanism of circ_0029589 in oxidized low-density lipoprotein (ox-LDL)-caused vascular smooth muscle cells (VSMCs) injury in vitro.

Main methods: VSMCs were challenged via ox-LDL to mimic atherosclerosis-like injury in vitro. Circ_0029589, microRNA-214-3p (miR-214-3p) and stromal interaction molecule 1 (STIM1) abundances were detected via quantitative reverse transcription polymerase chain reaction or western blot. Cell proliferation was investigated via cell viability, cycle, apoptosis and proliferation-associated protein levels. Cell migration and invasion were assessed via transwell analysis. The relationship between miR-214-3p and circ_0029589 or STIM1 was tested via dual-luciferase reporter analysis and RNA immunoprecipitation.

Key findings: Circ_0029589 level was enhanced in ox-LDL-challenged VSMCs. Circ_0029589 interference constrained cell proliferation, migration and invasion in ox-LDL-challenged VSMCs. miR-214-3p was targeted by circ_0029589 and miR-214-3p knockdown weakened the suppressive function of circ_0029589 silence on VSMCs proliferation, migration and invasion. STIM1 was targeted via miR-214-3p and miR-214-3p could suppress VSMCs proliferation, migration and invasion via decreasing STIM1. Moreover, circ_0029589 modulated STIM1 level by miR-214-3p.

Significance: Circ_0029589 knockdown repressed proliferation, migration and invasion of VSMCs challenged via ox-LDL by regulating miR-214-3p and STIM1, indicating that circ_0029589 might play important role in atherosclerosis.

Keywords: Atherosclerosis; Ox-LDL; STIM1; Vascular smooth muscle cells; hsa_circ_0029589; miR-214-3p.

MeSH terms

  • Apoptosis / physiology
  • Atherosclerosis / genetics*
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Cell Survival / physiology
  • Disease Progression
  • Humans
  • Lipoproteins, LDL / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / physiology
  • Neoplasm Invasiveness
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • Signal Transduction
  • Stromal Interaction Molecule 1 / genetics
  • Stromal Interaction Molecule 1 / metabolism*

Substances

  • Lipoproteins, LDL
  • MIRN214 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Circular
  • RNA, Long Noncoding
  • STIM1 protein, human
  • Stromal Interaction Molecule 1
  • oxidized low density lipoprotein