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Circular RNA circ_0010283 regulates the viability and migration of oxidized low?density lipoprotein?induced vascular smooth muscle cells via an miR?370?3p/HMGB1 axis in atherosclerosis.

ABSTRACT: Atherosclerosis is a disease during which the inside of an artery narrows due to the accumulation of plaque, and vascular smooth muscle cells (VSMCs) are involved in the progression of atherosclerosis. Circular RNAs (circRNAs) have been reported to be involved in the progression of atherosclerosis. However, the role of circ_0010283 in atherosclerosis progression remains unclear. The present study aimed to investigate the functions and the mechanism of circ_0010283 in oxidized low?density lipoprotein (ox?LDL)?induced VSMCs and to identify new potential biomarkers for the treatment of atherosclerosis. Cell viability and migration were examined by 3?(4,5?dimethylthiazol?2?yl)?2,5?diphenyltetrazolium bromide and Transwell assays. The relationship between microRNA (miR)?370?3p and circ_0010283 or high mobility group box 1 (HMGB1) was predicated by online software and confirmed by dual?luciferase reporter assay and RNA immunoprecipitation assay. The results of the present study demonstrated that the expression levels of circ_0010283 and HMGB1 were significantly upregulated in ox?LDL?induced VSMCs compared with those in VSMCs without ox?LDL induction, whereas the expression of miR?370?3p was downregulated. Knockdown of circ_0010283 suppressed VSMC viability and migration, as well as the expression of viability?associated proteins cyclin D1 and proliferating cell nuclear antigen, and migration?associated proteins matrix metalloproteinase 2 (MMP2) and MMP9 in ox?LDL?induced VSMCs compared with untreated VSMCs. In addition, miR?370?3p was demonstrated to be a target of circ_0010283 and to target HMGB1; thus, circ_0010283 regulated HMGB1 expression via miR?370?3p. Further experiments indicated that inhibition of miR?370?3p reversed the circ_0010283 silencing?mediated inhibitory effects on VMSC viability and migration. Additionally, the miR?370?3p?mediated suppressive effects on cell viability and migration were rescued by overexpression of HMGB1. In conclusion, circ_0010283 mediated cell viability and migration via a miR?370?3p/HMGB1 axis in ox?LDL?induced VSMCs.

SUBMITTER: Ding P

PROVIDER: S-EPMC7447304 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Circular RNA circ_0010283 regulates the viability and migration of oxidized low‑density lipoprotein‑induced vascular smooth muscle cells via an miR‑370‑3p/HMGB1 axis in atherosclerosis.

Ding Peng P Ding Yi Y Tian Ye Y Lei Xiaochun X

International journal of molecular medicine 20200812 4

Atherosclerosis is a disease during which the inside of an artery narrows due to the accumulation of plaque, and vascular smooth muscle cells (VSMCs) are involved in the progression of atherosclerosis. Circular RNAs (circRNAs) have been reported to be involved in the progression of atherosclerosis. However, the role of circ_0010283 in atherosclerosis progression remains unclear. The present study aimed to investigate the functions and the mechanism of circ_0010283 in oxidized low‑density lipopro ...[more]

PMID: 32945389

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Project description:BackgroundCircular RNAs (circRNAs) represent a class of non-coding RNAs (ncRNAs) which are widely expressed in mammals and tissue-specific, of which some could act as critical regulators in the atherogenesis of cerebrovascular disease. However, the underlying mechanisms by which circRNA regulates the ectopic phenotype of endothelial cells (ECs) in atherosclerosis remain largely elusive.MethodsCCK-8, transwell, wound healing and Matrigel assays were used to assess cell viability, migration and tube formation. QRT-qPCR and Immunoblotting were used to examine targeted gene expression in different groups. The binding sites of miR-370-3p (miR-370) with TGFβR2 or hsa_circ_0003204 (circ_0003204) were predicted using a series of bioinformatic tools, and validated using dual luciferase assay and RNA immunoprecipitation (RIP) assay. The localization of circ_0003204 and miR-370 in ECs were investigated by fluorescence in situ hybridization (FISH). Gene function and pathways were enriched through Metascape and gene set enrichment analysis (GSEA). The association of circ_0003204 and miR-370 in extracellular vesicles (EVs) with clinical characteristics of patients were investigated using multiple statistical analysis.ResultsCirc_0003204, mainly located in the cytoplasm of human aorta endothelial cells (HAECs), was upregulated in the ox-LDL-induced HAECs. Functionally, the ectopic expression of circ_0003204 inhibited proliferation, migration and tube formation of HAECs exposed to ox-LDL. Mechanically, circ_0003204 could promote protein expression of TGFβR2 and its downstream phosph-SMAD3 through sponging miR-370, and miR-370 targeted the 3' untranslated region (UTR) of TGFβR2. Furthermore, the expression of circ_0003204 in plasma EVs was upregulated in the patients with cerebral atherosclerosis, and represented a potential biomarker for diangnosis and prognosis of cerebrovascular atherogenesis.ConclusionsCirc_0003204 could act as a novel stimulator for ectopic endothelial inactivation in atherosclerosis and a potential biomarker for cerebral atherosclerosis.

Project description:BackgroundPrevious studies have reported the role of circular RNAs (circRNAs) in the progression of non-small-cell lung cancer (NSCLC). SWT1-derived circRNAs were confirmed to affect the apoptosis of cardiomyocytes; however, the biological functions of SWT1-derived circRNAs in cancers are still unknown. Here, we investigated the potential role of SWT1-derived circRNAs in NSCLC.MethodsWe used quantitative real-time polymerase chain reaction (qRT-PCR) to measure the expression of circSWT1 in NSCLC tissues and paired normal tissues. The potential functions of circSWT1 in tumor progression were assessed by CCK-8, colony formation, wound healing, and matrigel transwell assays in vitro and by xenograft tumor models in vivo. Next, epithelial-mesenchymal transition (EMT) was evaluated by western blotting, immunofluorescence, and immunohistochemistry (IHC). Moreover, circRIP, RNA pulldown assays, luciferase reporter gene assays, and FISH were conducted to illuminate the molecular mechanisms of circSWT1 via the miR-370-3p/SNAIL signal pathway. Then, we knocked out SNAIL in A549 and H1299 cells to identify the roles of circSWT1 in the progression and EMT of NSCLC through SNAIL. Finally, circSWT1 functions were confirmed in vivo using xenograft tumor models.ResultsCircSWT1 expression was significantly upregulated in NSCLC tissues, and high expression of circSWT1 predicted poor prognosis in NSCLC via survival analysis. In addition, overexpression of circSWT1 promoted the invasion and migration of NSCLC cells. Subsequently, we found that overexpression of circSWT1 induced EMT and that knockdown of circSWT1 inhibited EMT in NSCLC cells. Mechanistically, circSWT1 relieved the inhibition of downstream SNAIL by sponging miR-370-3p. Moreover, we found that these effects could be reversed by knocking out SNAIL. Finally, we verified that circSWT1 promoted NSCLC progression and EMT in xenograft tumor models.ConclusionCircSWT1 promoted the invasion, migration, and EMT of NSCLC. CircSWT1 could serve as a potential biomarker and a potential therapeutic target for NSCLC.

Project description:Few studies have addressed the mechanism by which circ_0010729 regulates hypoxia-induced cell injury in cardiovascular diseases. However, its role and its regulatory mechanism in myocardial infarction remain to be explored. Cell viability, cycle, apoptosis, and migration were analyzed using cell counting kit-8 assay, flow cytometry, caspase-3 activity assay kit and transwell assay, respectively. Tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) concentrations were examined by enzyme-linked immunosorbent assay. Glucose metabolism was calculated by detecting ATP production, glucose uptake and lactate production. Levels of circ_0010729, miR-370-3p and TNF Receptor Associated Factor 6 (TRAF6) were detected using quantitative real-time polymerase chain reaction or western blot. The direct interaction between circ_0010729 and TRAF6 or miR-370-3p was verified using dual-luciferase reporter assay and RNA immunoprecipitation assay. Under hypoxia condition, cardiomyocytes suffered from cell viability suppression, cell cycle arrest, cell apoptosis promotion, migration reduction, increase of inflammatory factor IL-6 and TNF-α, as well as glycolysis inhibition. Circ_0010729 expression was up-regulated in the cardiomyocytes at different hypoxia-exposed time points. Circ_0010729 knockdown protected cardiomyocytes against hypoxic dysfunction, while circ_0010729 overexpression showed inverse effects. MiR-370-3p was confirmed to directly bind to circ_0010729 or TRAF6. MiR-370-3p inhibition attenuated the protective effects of circ_0010729 knockdown on hypoxia-modulated cardiomyocyte dysfunction. MiR-370-3p restoration protected cardiomyocytes against hypoxic injury via targeting TRAF6. Besides, circ_0010729 indirectly regulated TRAF6 expression via miR-370-3p. This study demonstrated that circ_0010729 knockdown attenuated hypoxia-induced cardiomyocyte dysfunction via miR-370-3p/TRAF6 axis, indicating a potential therapeutic target for myocardial infarction.

Dataset Information

Circular RNA circ_0010283 regulates the viability and migration of oxidized low?density lipoprotein?induced vascular smooth muscle cells via an miR?370?3p/HMGB1 axis in atherosclerosis.

Publications

Circular RNA circ_0010283 regulates the viability and migration of oxidized low‑density lipoprotein‑induced vascular smooth muscle cells via an miR‑370‑3p/HMGB1 axis in atherosclerosis.

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