LAUSR

Atherosclerosis (AS) is a chronic inflammatory disorder. The aim of our study was to explore the role of circular RNA (circRNA) transmembrane 7 superfamily member 3 (circTM7SF3) in AS progression. Experiments were conducted using oxidized low-density lipoprotein (ox-LDL)-induced THP-1-derived macrophages and differentiated human monocyte-derived macrophages (hMDMs). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of circTM7SF3, its linear form TM7SF3, microRNA-206 (miR-206) and aspartyl (asparaginyl) β-hydroxylase (ASPH) messenger RNA (mRNA). Cell viability and apoptosis were examined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. Cell inflammation was analyzed by measuring the production of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) using enzyme-linked immunosorbent assay (ELISA) kits. Cell oxidative stress was assessed through analyzing the levels of oxidative stress markers using their corresponding commercial kits. Dual-luciferase reporter assay and RNA-pull down assay were used to confirm the interaction between miR-206 and circTM7SF3 or ASPH. The protein level of ASPH was examined by Western blot assay. CircTM7SF3 level was markedly increased in the serum samples of AS patients and ox-LDL-induced THP-1-derived macrophages compared with their matching counterparts. ox-LDL induced-damage in THP-1 cells was partly attenuated by the interference of circTM7SF3. MiR-206 was a downstream molecular target of circTM7SF3. Si-circTM7SF3-mediated effects in ox-LDL-induced THP-1-derived macrophages were partly ameliorated by the addition of anti-miR-206. MiR-206 directly interacted with ASPH mRNA. CircTM7SF3 silencing reduced the expression of ASPH partly through up-regulating miR-206 in THP-1-derived macrophages. ASPH overexpression partly counteracted the effects induced by miR-206 overexpression in ox-LDL-induced THP-1-derived macrophages. CircTM7SF3 contributed to ox-LDL-induced injury in AS cell model through up-regulating the expression of ASPH via targeting miR-206.