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

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.