Circular RNA testis-expressed 14 overexpression induces apoptosis and suppresses migration of ox-LDL-stimulated vascular smooth muscle cells via regulating the microRNA 6509-3p/thanatos-associated domain-containing apoptosis-associated protein 1 axis

Bioengineered. 2022 May;13(5):13150-13161. doi: 10.1080/21655979.2022.2070582.

Abstract

Atherosclerosis is a severe vascular disorder causing myocardial infarction, stroke, and gangrene. Circular RNA Testis-expressed 14 (hsa_circ_0107197, CircTEX14) is a newly discovered circRNA that may have a critical role in the pathogenesis of atherosclerosis. Here, we aimed to further explore the exact role of circRNA TEX14 in the cardiovascular system. Serum samples of atherosclerosis patients (n = 48) and healthy volunteers (n = 48) were collected to assess circTEX14 expressions. Quantitative reverse transcription-PCR (qRT-PCR), cell proliferation assay, migration assay, cell necrosis assay, Annexin staining, TUNEL assays, RNA immunoprecipitation (RIP) assays, dual-luciferase reporter assays, wound healing assays, and Western blot were performed to examine the roles of circTEX14, miR-6509-3p, and thanatos-associated domain-containing apoptosis-associated protein 1 (THAP1) in ox-LDL-stimulated vascular smooth muscle cells (VSMCs). We found that circTEX14 expressions were decreased and miR-6509-3p expressions were increased in the serum samples of atherosclerosis patients and ox-LDL-stimulated VSMCs. CircTEX14 overexpression inhibited proliferation and migration and enhanced apoptosis of VSMCs. CircTEX14 suppressed miR-6509-3p expressions through direct interaction. MiR-6509-3p or THAP1 knockdown reversed the effects of circTEX14 overexpression on proliferation, migration, and apoptosis of ox-LDL-stimulated VSMCs. In conclusion, circTEX14 inhibited proliferation and enhanced apoptosis via modulating miR-6509-3p/THAP1 in ox-LDL-stimulated VSMCs and might be a useful target for atherosclerosis treatment.

Keywords: CircRNA; THAP1; atherosclerosis; circTEX14; miR-6509-3p.

MeSH terms

  • Apoptosis / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Atherosclerosis* / metabolism
  • Cell Proliferation / genetics
  • DNA-Binding Proteins / metabolism
  • Humans
  • Lipoproteins, LDL
  • Male
  • MicroRNAs* / metabolism
  • Muscle, Smooth, Vascular / pathology
  • RNA, Circular / genetics
  • RNA, Long Noncoding* / genetics
  • Testis / metabolism
  • Testis / pathology
  • Transcription Factors / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • DNA-Binding Proteins
  • Lipoproteins, LDL
  • MicroRNAs
  • RNA, Circular
  • RNA, Long Noncoding
  • TEX14 protein, human
  • THAP1 protein, human
  • Transcription Factors
  • oxidized low density lipoprotein

Grants and funding

The author(s) reported there is no funding associated with the work featured in this article.