Abstract
BackgroundCircular RNAs (circRNAs) play critical roles in the development of atherosclerosis (AS). This study investigated the role of circMTO1 in the progression of AS.MethodsSerum samples from AS patients and healthy volunteers and vascular smooth muscle cells (VSMCs) were used as the study materials. The expressions of circMTO1 and miR-182-5p were measured by RT-qPCR. The effects of circMTO1, miR-182-5p, and RASA1 on VSMC proliferation and apoptosis were examined by MTT and BrdU assays and wound healing and flow cytometric analyses, respectively. Downstream target genes of circMTO1 and miR-182-5p were predicted using target gene prediction and screening and confirmed using a luciferase reporter assay. RASA1 expression was detected by RT-qPCR and Western blot.ResultscircMTO1 expression was decreased, while miR-182-5p expression was increased in human AS sera and oxidized low-density lipoprotein (ox-LDL)-stimulated VSMCs. CircMTO1 overexpression inhibited the proliferation and promoted the apoptosis of ox-LDL-stimulated VSMCs. CircMTO1 was found to be served as a sponge of miR-182-5p and RASA1 as a target of miR-182-5p. Moreover, circMTO1 acted as a ceRNA of miR-182-5p to enhance RASA1 expression. Furthermore, miR-182-5p overexpression and RASA1 knockdown reversed the effects of circMTO1 overexpression on the proliferation, migration, and apoptosis of ox-LDL-stimulated VSMCs.ConclusionCircMTO1 inhibited the proliferation and promoted the apoptosis of ox-LDL-stimulated VSMCs by regulating miR-182-5p/RASA1 axis. These results suggest that circMTO1 has potential in AS treatment.
Highlights
Circular RNAs play critical roles in the development of atherosclerosis (AS)
Studies have shown that a low concentration of Oxidized low-density lipoprotein (ox-LDL) can promote the proliferation of vascular smooth muscle cells (VSMCs), while a high concentration of ox-LDL can promote the apoptosis of VSMCs (Wang et al 2019a)
CircMTO1 expression was reduced in the serum of AS patients and ox‐LDL‐stimulated VSMCs Firstly, circMTO1 expression in serum of AS patients and ox-LDL-stimulated VSMCs was examined
Summary
Circular RNAs (circRNAs) play critical roles in the development of atherosclerosis (AS). This study investigated the role of circMTO1 in the progression of AS. Arteriosclerosis (AS) has become one of the major causes of increased mortality and incidence rates of cardiovascular and cerebrovascular diseases worldwide (Lippincott and Wilkins 2017; Tabib et al 2017). It has seriously affected the quality of life of the middle-aged and the. It is well known that the proliferation of VSMCs is the common pathogenesis of cardiovascular and cerebrovascular diseases. In this study, ox-LDL was used to establish the proliferation model of VSMCs to explore the mechanism of atherosclerosis further
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